Design of protein-ligand binding based on the molecular-mechanics energy model

<!DOCTYPE html> <html lang="en" > <head itemscope itemtype="http://schema.org/WebPage" prefix="og: http://ogp.me/ns#" > <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge">  <meta name="HandheldFriendly" content="True"> <meta name="MobileOptimized" content="320"> <meta name="viewport" content="width=device-width, initial-scale=1.0"> <link rel="preconnect" href="https://cdn.ncbi.nlm.nih.gov"> <link rel="preconnect" href="https://www.ncbi.nlm.nih.gov"> <link rel="preconnect" href="https://www.google-analytics.com"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.5ecf62baa0fa.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.452c70ce66f7.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.7bf600913d6e.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.0bfa59184c7a.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.b576742ffc3e.css" type="text/css"> <title>Design of protein-ligand binding based on the molecular-mechanics energy model - PubMed</title> <link rel="preload" as="font" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/uswds/dist/fonts/merriweather-bold-webfont.woff2" type="font/woff2" crossorigin />  <link rel="shortcut icon" type="image/ico" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon.ico" /> <link rel="icon" type="image/png" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon.png" />  <link rel="icon" type="image/png" sizes="192x192" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-192.png" />  <link rel="apple-touch-icon-precomposed" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-57.png">  <link rel="apple-touch-icon-precomposed" sizes="72x72" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-72.png">  <link rel="apple-touch-icon-precomposed" sizes="114x114" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-114.png">  <link rel="apple-touch-icon-precomposed" sizes="144x144" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-144.png">  <meta name="ncbi_sg_optimize_id" content="">  <meta name="theme-color" content="#20558a">  <meta name="referrer" content="origin-when-cross-origin"> <meta name="ncbi_pinger_gtm_track" content="true"/>  <meta name="ncbi_app" content="pubmed" /> <meta name="ncbi_db" content="pubmed" /> <meta name="ncbi_phid" content="79F0000142671E9500002E5508F2A355.1.m_6" /> <meta name="ncbi_pinger_stat_url" content="https://www.ncbi.nlm.nih.gov/stat" /> <meta name="log_category" content="literature" /> <meta name="ncbi_cost_center" content="pubmed" />  <meta name="ncbi_pdid" content="abstract" /> <meta name="log_op" content="retrieve" /> <meta name="uid" content="18514737" /> <meta name="ncbi_uid" content="18514737" /> <meta name="log_displayeduids" content="18514737" /> <meta name="log_source_db" content="pubmed,pmc" /> <meta name="log_icons_present" content="true" />  <meta name="description" content="While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual laboratories. Here we show that a standard molecular-mechanics potential energy function without any modifications can …"><meta name="keywords" content="pmid:18514737, PMC2569001, doi:10.1016/j.jmb.2008.04.001, Research Support, N.I.H., Extramural, F Edward Boas, Pehr B Harbury, Algorithms, Amino Acid Sequence, Binding Sites, Computer Simulation, Crystallography, X-Ray, Escherichia coli Proteins / chemistry*, Escherichia coli Proteins / genetics, Escherichia coli Proteins / metabolism*, Ligands*, Models, Biological*, Molecular Sequence Data, Molecular Structure, Periplasmic Binding Proteins / chemistry*, Periplasmic Binding Proteins / genetics, Periplasmic Binding Proteins / metabolism*, Protein Binding, Protein Conformation, Protein Interaction Mapping*, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Design of protein-ligand binding based on the molecular-mechanics energy model - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/18514737/"><meta property="og:description" content="While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual laboratories. Here we show that a standard molecular-mechanics potential energy function without any modifications can …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Design of protein-ligand binding based on the molecular-mechanics energy model - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/18514737/"><meta name="twitter:description" content="While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual laboratories. Here we show that a standard molecular-mechanics potential energy function without any modifications can …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">  <link rel="search" type="application/opensearchdescription+xml" href="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/opensearch.xml" title="PubMed search">  <noscript> <link rel="stylesheet" type="text/css" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/core/no-script.css"> </noscript> <meta name="citation_title" content="Design of protein-ligand binding based on the molecular-mechanics energy model"> <meta name="citation_authors" content="Boas FE;Harbury PB;"> <meta name="citation_date" content="07/04/2008"> <meta name="citation_publisher" content="J Mol Biol"> <meta name="citation_journal_title" content="Journal of molecular biology"> <meta name="citation_pmid" content="18514737"> <meta name="citation_abstract_html_url" content="https://pubmed.ncbi.nlm.nih.gov/18514737/"> <meta name="citation_volume" content="380"> <meta name="citation_issue" content="2"> <meta name="citation_doi" content="10.1016/j.jmb.2008.04.001"> <meta name="citation_issn" content="1089-8638"> <link rel="canonical" href="https://pubmed.ncbi.nlm.nih.gov/18514737/" /> </head> <body > <noscript> <div class="no-script-banner" id="no-script-banner"> <div class="warning-message"> <div class="warning-message-text"> This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! </div> </div> </div> </noscript> <div class="no-session-banner" id="no-session-banner" hidden> <div class="warning-message"> <div class="warning-message-text"> Clipboard, Search History, and several other advanced features are temporarily unavailable. </div> <button class="close-banner-button" title="Close Clipboard and Search History not available warning banner" ref="linksrc=close_no_session_banner" aria-controls="no-session-banner" aria-label="Close Clipboard and Search History not available warning banner" aria-expanded="true"> </button> </div> </div> <a class="usa-skipnav" href="#article-details"> Skip to main page content </a>  <section class="usa-banner"> <div class="usa-accordion"> <header class="usa-banner-header"> <div class="usa-grid usa-banner-inner"> <img src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png" alt="U.S. flag" /> <p>An official website of the United States government</p> <button class="usa-accordion-button usa-banner-button" aria-expanded="false" aria-controls="gov-banner-top" > <span class="usa-banner-button-text">Here's how you know</span> </button> </div> </header> <div class="usa-banner-content usa-grid usa-accordion-content" id="gov-banner-top" > <div class="usa-banner-guidance-gov usa-width-one-half"> <img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg" alt="Dot gov" /> <div class="usa-media_block-body"> <p> <strong>The .gov means it’s official.</strong> <br /> Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site. </p> </div> </div> <div class="usa-banner-guidance-ssl usa-width-one-half"> <img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg" alt="Https" /> <div class="usa-media_block-body"> <p> <strong>The site is secure.</strong> <br /> The <strong>https://</strong> ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. </p> </div> </div> </div> </div> </section> <div class="usa-overlay"></div> <header class="ncbi-header" role="banner" data-section="Header"> <div class="usa-grid"> <div class="usa-width-one-whole"> <div class="ncbi-header__logo"> <a href="https://www.ncbi.nlm.nih.gov/" class="logo" aria-label="NCBI Logo" data-ga-action="click_image" data-ga-label="NIH NLM Logo"> <img src="https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg" alt="NIH NLM Logo" /> </a> </div> <div class="ncbi-header__account"> <a id="account_login" href="https://account.ncbi.nlm.nih.gov" class="usa-button header-button" style="display:none" data-ga-action="open_menu" data-ga-label="account_menu">Log in</a> <button id="account_info" class="header-button" style="display:none" aria-controls="account_popup"> <span class="fa fa-user" aria-hidden="true"></span> <span class="username desktop-only" aria-hidden="true" id="uname_short"></span> <span class="sr-only">Show account info</span> </button> </div> <div class="ncbi-popup-anchor"> <div class="ncbi-popup account-popup" id="account_popup" aria-hidden="true"> <div class="ncbi-popup-head"> <button class="ncbi-close-button" data-ga-action="close_menu" data-ga-label="account_menu"><span class="fa fa-times"></span><span class="usa-sr-only">Close</span></button> <h4>Account</h4> </div> <div class="account-user-info"> Logged in as:<br/> <b><span class="username" id="uname_long">username</span></b> </div> <div class="account-links"> <ul class="usa-unstyled-list"> <li><a id="account_myncbi" href="/myncbi/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_myncbi">Dashboard</a></li> <li><a id="account_pubs" href="/myncbi/collections/bibliography/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_pubs">Publications</a></li> <li><a id="account_settings" href="/account/settings/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_settings">Account settings</a></li> <li><a id="account_logout" href="/account/signout/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_logout">Log out</a></li> </ul> </div> </div> </div> </div> </div> </header> <div role="navigation" aria-label="access keys"> <a id="nws_header_accesskey_0" href="https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys" class="usa-sr-only" accesskey="0" tabindex="-1">Access keys</a> <a id="nws_header_accesskey_1" href="https://www.ncbi.nlm.nih.gov" class="usa-sr-only" accesskey="1" tabindex="-1">NCBI Homepage</a> <a id="nws_header_accesskey_2" href="/myncbi/" class="set-base-url usa-sr-only" accesskey="2" tabindex="-1">MyNCBI Homepage</a> <a id="nws_header_accesskey_3" href="#maincontent" class="usa-sr-only" accesskey="3" tabindex="-1">Main Content</a> <a id="nws_header_accesskey_4" href="#" class="usa-sr-only" accesskey="4" tabindex="-1">Main Navigation</a> </div> <section data-section="Alerts"> <div class="ncbi-alerts-placeholder"></div> </section>  <a id="maincontent" aria-label="Main page content below" role="navigation"></a> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <form action="/" method="get" autocomplete="off" class="usa-search usa-search-big search-form content-page-layout" id="search-form" role="search"> <div class="inner-wrap"> <a class="pubmed-logo" aria-label="Pubmed Logo" href="/" data-ga-category="featured_link" data-ga-action="pubmed_logo"> <img src="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/core/images/pubmed-logo-blue.svg" alt="pubmed logo" /> </a> <a href="#" class="search-input-trigger" data-alt-title="Hide search bar" title="Show search bar" aria-label="Show search bar"> </a> <div role="search" class="search-input"> <div class="form-field "> <label class="usa-sr-only" for="id_term"> Search: </label> <input type="search" name="term" data-skip-ie-scroll-to-top="" data-replace-term-with-exact="" data-exact-query="" placeholder="" class="term-input" required="required" id="id_term"/><a href="#" class="clear-btn" aria-label="Clear search input" title="Clear search input" role="button" data-pinger-ignore></a><button type="submit" class="search-btn" aria-label="Search" disabled data-pinger-ignore><span class="usa-search-submit-text">Search</span></button> </div> </div>   <div class="search-links-wrapper content-page-layout"> <div class="search-links"> <a href="/advanced/" class="search-input-link adv-search-link" data-ga-category="featured_link" data-ga-action="adv_search">Advanced</a> <a href="/clipboard/" class="search-input-link clipboard-link hidden" data-ga-category="featured_link" data-ga-action="clipboard"> Clipboard <span class="amount-in-clipboard"></span> </a> </div> <span class="search-input-link user-guide-link" role="navigation" aria-label="User guide"> <a href="/help/" data-ga-category="featured_link" data-ga-action="user_guide"> User Guide </a> </span> </div> </div> </form> <div id="article-page-header"> <div id="article-top-actions-bar" class="article-top-actions-bar"> <div class="inner-wrap"> <div class="actions-container"> <div class="return-to-search"> </div> <div class="multiple-results-actions " role="region" aria-label="save, email, send to"> <button id="save-results-panel-trigger" type="button" class="save-results save-results-panel-trigger" aria-expanded="false" aria-controls="save-action-panel" data-ga-category="save_share" data-ga-action="save" data-ga-label="open"> Save </button><button id="email-results-panel-trigger" type="button" class="email-results email-results-panel-trigger" aria-expanded="false" aria-controls="email-action-panel" data-ga-category="save_share" data-ga-action="email" data-ga-label="open"> Email </button><div class="more-actions dropdown-block"><button id="more-actions-trigger" type="button" class="trigger more-actions-trigger" ref="linksrc=show_moreactions_btn" aria-label="Send to" aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link " href="#" role="button" data-ga-category="save_share" data-ga-action="clipboard" data-ga-label="send"> Clipboard </a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18514737%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18514737%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div> </div> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> <span class="button-label">Display options</span> </button> <div class="dropdown" hidden> <div class="title"> Display options </div> <div class="content"> <div class="format-container"> <span class="option-label"> Format </span> <select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format"> <option value="abstract">Abstract</option> <option value="pubmed">PubMed</option> <option value="pmid">PMID</option> </select> </div> </div> </div> </div> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> </div> </div> </div> <div id="article-panels-container" class="article-panels-container"> <div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Save citation to file </h2> <form id="save-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <div class="action-panel-control-wrap"> <label for="save-action-format" class="action-panel-label"> Format: </label> <select id="save-action-format" name="results-format" class="action-panel-selector"> <option value="summary-text">Summary (text)</option> <option value="pubmed-text">PubMed</option> <option value="pmid">PMID</option> <option value="abstract">Abstract (text)</option> <option value="csv">CSV</option> </select> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="save" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Save citations to file' panel" ref="linksrc=close_save_panel" aria-controls="save-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="save" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="email-action-panel" class="email-action-panel action-panel" aria-hidden="true" data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback" data-recaptcha-enabled="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Email citation </h2> <form id="email-action-panel-form" class="action-panel-content action-form" action="/send-email/" data-by-search-action="/results-export-email-by-search-data/" data-by-ids-action="/send-email/" data-by-search-method="post" data-by-ids-method="post" method="post" > <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <div class="action-panel-control-wrap"> <span class="action-panel-label"> Subject: </span> <span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 18514737 - PubMed</span> <input type="hidden" name="email-subject" value="1 selected item: 18514737"/> <input type="hidden" name="email-subject-hash" value="8fd63ff96d354cd7853ee2ffd5a092e63dcf589c8760f6b2e0bdf44dce114caf"/> </div> <div class="action-panel-control-wrap"> <label for="email-to" class="action-panel-label required-field-asterisk"> To: </label> <input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required> </div> <div class="action-panel-control-wrap"> <label for="email-from" class="action-panel-label"> From: </label> <input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256"> </div> <div class="action-panel-control-wrap"> <label for="email-citation-format" class="action-panel-label"> Format: </label> <select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format"> <option selected="selected" value="summary">Summary</option> <option value="summary-text">Summary (text)</option> <option value="abstract">Abstract</option> <option value="abstract-text">Abstract (text)</option> </select> </div> <div class="include-supplemental-container"> <input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental"> <label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label> </div> <div class="form-field recaptcha "> <div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div> </div> <div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="email" data-ga-label="send"> Send email </button> <button class="action-panel-cancel" aria-label="Close 'Email citations' panel" ref="linksrc=close_email_panel" aria-controls="email-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="email" data-ga-label="cancel"> Cancel </button> </div> <input type="hidden" name="email-search-details" value="" /> <input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" /> </form> </div> </div> <div id="collections-action-panel" class="collections-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-collections-open-panel-enabled="false" data-collections-open-panel-url-hash="#open-collections-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to Collections </h3> <form id="collections-action-panel-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-myncbi-max-collection-name-length="100" data-add-to-collection-max-amount="1000" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <div class="choice-group" role="radiogroup"> <ul class="radio-group-items"> <li> <input type="radio" id="collections-action-panel-new" class="collections-new" name="collections" value="new" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_new"> <label for="collections-action-panel-new">Create a new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="18514737"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://linkinghub.elsevier.com/retrieve/pii/S0022-2836(08)00408-7" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=18514737&db=pubmed&nlmid=2985088R" title="See full text options at Elsevier Science" data-ga-category="full_text" data-ga-action="Elsevier Science" data-ga-label="18514737" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="full text provider logo"><span class="text"> Elsevier Science </span></a><a class="link-item pmc " href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/18514737/" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=18514737&db=pubmed&nlmid=2985088R" title="Free full text at PubMed Central" data-ga-category="full_text" data-ga-action="PMC" data-ga-label="18514737" ><span class="text"> Free PMC article </span></a> </div> </div> <div class="short-view"> <a href="#" class="full-text-links-button full-text-links-dialog-trigger"> Full text links </a> </div> </div> <div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/18514737/citations/" data-citation-style="nlm" data-pubmed-format-link="/18514737/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="18514737" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger" aria-label="Save article in MyNCBI collections." data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_button" data-collections-open-dialog-enabled="false" data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18514737%2F%23open-collections-dialog" data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog" class="dialog collections-dialog" aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-myncbi-max-collection-name-length="100" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="sidebar-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="social-sharing"> <h3 class="title"> Share </h3> <ul class="social-sharing-links usa-unstyled-list"> <li> <a href="http://twitter.com/intent/tweet?text=Design%20of%20protein-ligand%20binding%20based%20on%20the%20molecular-mechanics%20energy%20model%20https%3A//pubmed.ncbi.nlm.nih.gov/18514737/" class="share-link share-link-twitter" rel="noreferrer noopener" target="Pubmed-Social-Media-Share-Popup" title="Share article on Twitter" data-ga-category="save_share" data-ga-action="social" data-ga-label="twitter"></a> </li> <li> <a href="http://www.facebook.com/sharer/sharer.php?u=https%3A//pubmed.ncbi.nlm.nih.gov/18514737/" class="share-link share-link-facebook" rel="noreferrer noopener" target="Pubmed-Social-Media-Share-Popup" title="Share article on Facebook" data-ga-category="save_share" data-ga-action="social" data-ga-label="fb"></a> </li> <li> <div class="share-permalink"> <button class="trigger" title="Show article permalink" ref="linksrc=show_permalink_btn"> </button> <div class="dropdown" hidden> <div class="title"> Permalink </div> <div class="content"> <input type="text" class="permalink-text" value="https://pubmed.ncbi.nlm.nih.gov/18514737/" aria-label="Article permalink"/><button class="permalink-copy-button usa-button-primary" title="Copy article permalink" data-ga-category="save_share" data-ga-action="link" data-ga-label="copy_link"><span class="button-title">Copy</span></button> </div> </div> </div> </li> </ul> </div> <nav class="page-navigator" role="navigation" aria-label="Page navigation"> <div class="full-view"> <h3 class="title"> Page navigation </h3> <ul class="items-list"> <li class="heading "> <a href="#heading" aria-label="navigate to Title & authors section" data-ga-category="page_nav" data-ga-action="heading"> Title & authors </a> </li> <li class="abstract "> <a href="#abstract" aria-label="navigate to Abstract section" data-ga-category="page_nav" data-ga-action="abstract"> Abstract </a> </li> <li class="figures "> <a href="#figures" aria-label="navigate to Figures section" data-ga-category="page_nav" data-ga-action="figures"> Figures </a> </li> <li class="similar "> <a href="#similar" aria-label="navigate to Similar articles section" data-ga-category="page_nav" data-ga-action="similar"> Similar articles </a> </li> <li class="citedby "> <a href="#citedby" aria-label="navigate to Cited by section" data-ga-category="page_nav" data-ga-action="citedby"> Cited by </a> </li> <li class="references "> <a href="#references" aria-label="navigate to References section" data-ga-category="page_nav" data-ga-action="references"> References </a> </li> <li class="publication-types "> <a href="#publication-types" aria-label="navigate to Publication types section" data-ga-category="page_nav" data-ga-action="publication-types"> Publication types </a> </li> <li class="mesh-terms "> <a href="#mesh-terms" aria-label="navigate to MeSH terms section" data-ga-category="page_nav" data-ga-action="mesh-terms"> MeSH terms </a> </li> <li class="substances "> <a href="#substances" aria-label="navigate to Substances section" data-ga-category="page_nav" data-ga-action="substances"> Substances </a> </li> <li class="related-links "> <a href="#related-links" aria-label="navigate to Related information section" data-ga-category="page_nav" data-ga-action="related-links"> Related information </a> </li> <li class="grants "> <a href="#grants" aria-label="navigate to Grants and funding section" data-ga-category="page_nav" data-ga-action="grants"> Grants and funding </a> </li> <li class="linkout "> <a href="#linkout" aria-label="navigate to LinkOut - more resources section" data-ga-category="page_nav" data-ga-action="linkout"> LinkOut - more resources </a> </li> </ul> </div> <select class="short-view" autocomplete="off" title="navigate to selected section" aria-label="Navigate to page section"> <option value="heading">Title & authors</option> <option value="abstract">Abstract</option> <option value="figures">Figures</option> <option value="similar">Similar articles</option> <option value="citedby">Cited by</option> <option value="references">References</option> <option value="publication-types">Publication types</option> <option value="mesh-terms">MeSH terms</option> <option value="substances">Substances</option> <option value="related-links">Related information</option> <option value="grants">Grants and funding</option> <option value="linkout">LinkOut - more resources</option> </select> </nav> </div> </aside> <main class="article-details" id="article-details">   <header class="heading" id="heading"> <div class="full-view" id="full-view-heading"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="full-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Journal of molecular biology" tabindex="0" aria-controls="full-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Journal of molecular biology" data-pinger-ignore> J Mol Biol </button><div id="full-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Journal of molecular biology"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22J+Mol+Biol%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22J+Mol+Biol%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=J Mol Biol" data-ga-category="search" data-ga-action="journal_link" data-ga-label="J Mol Biol"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Mol+Biol%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="J Mol Biol"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"J Mol Biol"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"J Mol Biol"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2008 Jul 4;380(2):415-24.</span> </div> <span class="citation-doi"> doi: 10.1016/j.jmb.2008.04.001. </span> <span class="secondary-date"> Epub 2008 Apr 8. </span> </div> <h1 class="heading-title"> Design of protein-ligand binding based on the molecular-mechanics energy model </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Boas+FE&cauthor_id=18514737" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="F Edward Boas">F Edward Boas</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Biochemistry, Stanford University School of Medicine, Beckman B437, 279 Campus Drive West, Stanford, CA 94305-5307, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Harbury+PB&cauthor_id=18514737" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Pehr B Harbury">Pehr B Harbury</a></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/18514737/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div class="affiliations"> <h3 class="title"> Affiliation </h3> <ul class="item-list"> <li data-affiliation-id="full-view-affiliation-1" id="full-view-affiliation-1" ><sup class="key">1</sup> Department of Biochemistry, Stanford University School of Medicine, Beckman B437, 279 Campus Drive West, Stanford, CA 94305-5307, USA.</li> </ul> </div> </div> </div> <ul class="identifiers" id="full-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">18514737</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC2569001&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2569001/" data-ga-category="full_text" data-ga-action="PMCID" > PMC2569001 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1016/j.jmb.2008.04.001&id_type=DOI" href="https://doi.org/10.1016/j.jmb.2008.04.001" data-ga-category="full_text" data-ga-action="DOI" > 10.1016/j.jmb.2008.04.001 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <h1 class="heading-title"> Design of protein-ligand binding based on the molecular-mechanics energy model </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">F Edward Boas</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> J Mol Biol<span class="citation-separator">.</span> </span> <span class="date"> <time class="citation-year" datetime="2008">2008</time><span class="citation-separator">.</span> </span> </div> <div class="more-article-details-section with-display-settings"> <button class="more-article-details" id="toggle-article-details" data-alt-text="Hide details" ref="linksrc=toggle_article_details" aria-controls="full-article-details" aria-expanded="false" data-fetch-url="/18514737/long-authors/" data-id-prefix=""> <span class="title">Show details</span> </button> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> <span class="button-label">Display options</span> </button> <div class="dropdown" hidden> <div class="title"> Display options </div> <div class="content"> <div class="format-container"> <span class="option-label"> Format </span> <select name="format" data-initial-value="abstract" aria-label="Display format" id="mobile-display-format"> <option value="abstract">Abstract</option> <option value="pubmed">PubMed</option> <option value="pmid">PMID</option> </select> </div> </div> </div> </div> </div> <div class="extended-article-details" id="full-article-details" aria-hidden="true"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="short-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Journal of molecular biology" tabindex="0" aria-controls="short-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Journal of molecular biology" data-pinger-ignore> J Mol Biol </button><div id="short-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Journal of molecular biology"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22J+Mol+Biol%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22J+Mol+Biol%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=J Mol Biol" data-ga-category="search" data-ga-action="journal_link" data-ga-label="J Mol Biol"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Mol+Biol%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="J Mol Biol"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"J Mol Biol"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"J Mol Biol"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2008 Jul 4;380(2):415-24.</span> </div> <span class="citation-doi"> doi: 10.1016/j.jmb.2008.04.001. </span> <span class="secondary-date"> Epub 2008 Apr 8. </span> </div> <div class="expanded-authors" id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Boas+FE&cauthor_id=18514737" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="F Edward Boas">F Edward Boas</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Biochemistry, Stanford University School of Medicine, Beckman B437, 279 Campus Drive West, Stanford, CA 94305-5307, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Harbury+PB&cauthor_id=18514737" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Pehr B Harbury">Pehr B Harbury</a></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliation </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Department of Biochemistry, Stanford University School of Medicine, Beckman B437, 279 Campus Drive West, Stanford, CA 94305-5307, USA.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">18514737</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC2569001&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2569001/" data-ga-category="full_text" data-ga-action="PMCID" > PMC2569001 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1016/j.jmb.2008.04.001&id_type=DOI" href="https://doi.org/10.1016/j.jmb.2008.04.001" data-ga-category="full_text" data-ga-action="DOI" > 10.1016/j.jmb.2008.04.001 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/18514737/citations/" data-citation-style="nlm" data-pubmed-format-link="/18514737/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual laboratories. Here we show that a standard molecular-mechanics potential energy function without any modifications can be used to engineer protein-ligand binding. A molecular-mechanics potential is used to reconstruct the coordinates of various binding sites with an average root-mean-square error of 0.61 A and to reproduce known ligand-induced side-chain conformational shifts. Within a series of 34 mutants, the calculation can always distinguish between weak (K(d)>1 mM) and tight (K(d)<10 microM) binding sequences. Starting from partial coordinates of the ribose-binding protein lacking the ligand and the 10 primary contact residues, the molecular-mechanics potential is used to redesign a ribose-binding site. Out of a search space of 2 x 10(12) sequences, the calculation selects a point mutant of the native protein as the top solution (experimental K(d)=17 microM) and the native protein as the second best solution (experimental K(d)=210 nM). The quality of the predictions depends on the accuracy of the generalized Born electrostatics model, treatment of protonation equilibria, high-resolution rotamer sampling, a final local energy minimization step, and explicit modeling of the bound, unbound, and unfolded states. The application of unmodified molecular-mechanics potentials to protein design links two fields in a mutually beneficial way. Design provides a new avenue for testing molecular-mechanics energy functions, and future improvements in these energy functions will presumably lead to more accurate design results. </p> </div> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/604d7c76b845/nihms57945f1.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="1050" data-image-height="697" data-image-alt="Figure 1" data-pmc-id="PMC2569001" data-figure-id="F1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/a246133f09d4/nihms57945f1.gif" alt="Figure 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="1050"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="697"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><p> Simplified schematic of the protein… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><p> Simplified schematic of the protein design algorithm. (a) Setting up a design calculation.… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1 </strong> <div class="figure-caption-contents">Simplified schematic of the protein design algorithm. (a) Setting up a design calculation. The design calculation is based on a scaffold protein (gray) with a known crystal structure, and a set of design positions (red). Possible ligand poses (green) and side chain conformations (blue) for each amino acid at each position are constructed. The right panel shows multiple side chain rotamers modeled at one design position, and two alternative ligand poses. Interaction energies between the possible ligand poses and the possible side chain conformations are precomputed. (b) Running a design calculation. The design procedure involves separate sequence optimization (to find sequences that bind ribose) and structural optimization (to determine the binding constant and stability of each sequence). In the RBP-ribose redesign, we search a space of 2×10<sup>12</sup> sequences and an average of 5×10<sup>28</sup> conformations per sequence.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/f1a601bb1afa/nihms57945f2.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="750" data-image-height="601" data-image-alt="Figure 2" data-pmc-id="PMC2569001" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/0b612e4640e8/nihms57945f2.gif" alt="Figure 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="750"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="601"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><p> Higher rotamer resolution improves structural… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><p> Higher rotamer resolution improves structural predictions for the RBP binding site (PDB code:… </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2 </strong> <div class="figure-caption-contents">Higher rotamer resolution improves structural predictions for the RBP binding site (PDB code: 2DRI). Δ Energy is the difference in potential energy between the calculated structure and the crystal structure, after both have been subjected to local energy minimization. RMS error is the root-mean-square deviation between the calculated and crystallographic coordinates of the repacked atoms, comprising the ligand and ten active site side chains. The phenylalanine rotamers from each rotamer library are shown to illustrate the sampling resolution. The lowest resolution rotamer library shown is the Richardson penultimate rotamer library with protonation states added for His, Asp, and Glu. The other rotamer libraries were derived by clustering side chain conformations in high resolution crystal structures from the Protein Data Bank (see Supporting Information).</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/7fdd112cdf16/nihms57945f3.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="1050" data-image-height="570" data-image-alt="Figure 3" data-pmc-id="PMC2569001" data-figure-id="F3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/7b109991c733/nihms57945f3.gif" alt="Figure 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="1050"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="570"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><p> Prediction of binding site coordinates.… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><p> Prediction of binding site coordinates. Starting from crystal structures stripped of the ligand… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3 </strong> <div class="figure-caption-contents">Prediction of binding site coordinates. Starting from crystal structures stripped of the ligand and the contacting residues, the active site was reconstructed by finding the lowest energy arrangement of the ligand and side chains. For ABP-arabinose (PBD code: 6ABP), the coordinates of the arabinose and 15 contacting residues (10, 14, 16, 17, 64, 89, 90, 108, 145, 147, 151, 204, 205, 232, 259) were predicted using 6028 rotamers per position and 4111 ligand poses. For RBP-ribose (PDB code: 2DRI), the coordinates of ribose and 10 contacting residues (13, 15, 16, 89, 90, 141, 164, 190, 215, 235) were predicted using 5449 rotamers per position, and 4639 ligand poses.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/7e349dee17be/nihms57945f4.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="1050" data-image-height="424" data-image-alt="Figure 4" data-pmc-id="PMC2569001" data-figure-id="F4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/87a43abc4043/nihms57945f4.gif" alt="Figure 4" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="1050"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="424"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><p> Prediction of binding site coordinates… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><p> Prediction of binding site coordinates for bevacizumab-VEGF (1BJ1), unbound VEGF (2VPF), and unbound… </p></div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4 </strong> <div class="figure-caption-contents">Prediction of binding site coordinates for bevacizumab-VEGF (1BJ1), unbound VEGF (2VPF), and unbound RBP (1URP). For bevacizumab-VEGF, the following 23 residues were repacked, using 6028 rotamers per position: V17, V21, W48, W79, W81, W82, W83, W91, W93, H28, H30, H31, H32, H54, H55, H99, H101, H102, H103, H105, H106, H107, H108. V and W are VEGF chains, H and L are antibody heavy and light chains. For unbound VEGF and RBP, the same set of residues were predicted as the bound structure.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="4" data-label-slug="figure-5"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/8b9b8d486531/nihms57945f5.jpg" itemprop="contentUrl" aria-describedby="figure-caption-4" role="button" data-image-width="1050" data-image-height="630" data-image-alt="Figure 5" data-pmc-id="PMC2569001" data-figure-id="F5"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-4" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/41e69cea3e0b/nihms57945f5.gif" alt="Figure 5" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="1050"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="630"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 5 </p> </strong> <div class="figure-caption-contents"><p> Prediction of side chain conformational… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 5 </p> </strong> <div class="figure-caption-contents"><p> Prediction of side chain conformational shifts in RBP upon binding ribose, or VEGF… </p></div> </div> <figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 5 </strong> <div class="figure-caption-contents">Prediction of side chain conformational shifts in RBP upon binding ribose, or VEGF upon binding bevacizumab. The five largest experimentally observed conformational shifts are shown for each protein. The residues were superimposed by aligning the backbone amide nitrogen, alpha carbon, and carbonyl carbon. * denotes correct predictions, where the unbound/bound predictions are closest to the unbound/bound crystallographic coordinates, respectively.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="5" data-label-slug="figure-6"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/598944106d65/nihms57945f6.jpg" itemprop="contentUrl" aria-describedby="figure-caption-5" role="button" data-image-width="1050" data-image-height="408" data-image-alt="Figure 6" data-pmc-id="PMC2569001" data-figure-id="F6"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-5" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/0677ab8d4896/nihms57945f6.gif" alt="Figure 6" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="1050"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="408"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 6 </p> </strong> <div class="figure-caption-contents"><p> Predicting dissociation energies. (a) Calculated… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 6 </p> </strong> <div class="figure-caption-contents"><p> Predicting dissociation energies. (a) Calculated stability and dissociation energy distinguish the native sequence… </p></div> </div> <figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 6 </strong> <div class="figure-caption-contents">Predicting dissociation energies. (a) Calculated stability and dissociation energy distinguish the native sequence (×) from 1000 scrambled sequences (♦) for ABP and RBP. Sequences predicted to be more then 10 kcal/mol destabilized relative to the native are shown in gray. (b) Predicting relative dissociation energies of mutants. The graph shows data on mutants of ABP binding to arabinose. Experimental data are from reference and from measurements reported in Supporting Table 6. An experimental dissociation energy of zero means that there was no detectable binding. Calculations were performed using 6ABP as the scaffold structure for both the bound and unbound states, with 6028 rotamers per position. Coordinates of the fifteen primary ligand contacts and of residues 20 and 235 were optimized. The circled points are predicted to be destabilized by more than 10 kcal/mol relative to the native.</div> </figcaption> </figure> <figure class="figure-item tail" itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="6" data-label-slug="figure-7"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/ace92e72eca6/nihms57945f7.jpg" itemprop="contentUrl" aria-describedby="figure-caption-6" role="button" data-image-width="1023" data-image-height="678" data-image-alt="Figure 7" data-pmc-id="PMC2569001" data-figure-id="F7"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-6" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5572/2569001/5039092d8a69/nihms57945f7.gif" alt="Figure 7" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="1023"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="678"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 7 </p> </strong> <div class="figure-caption-contents"><p> Redesigning the ribose binding site… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 7 </p> </strong> <div class="figure-caption-contents"><p> Redesigning the ribose binding site in RBP. Positions identical to the native are… </p></div> </div> <figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 7 </strong> <div class="figure-caption-contents">Redesigning the ribose binding site in RBP. Positions identical to the native are highlighted in yellow. The figure shows the best sequence as a function of the number of sequences considered, using either the mean field dissociation energy as the criterion (blue trajectories) or alternatively the dissociation energy calculated using minimized structures (red trajectories). All sequences with a mean field dissociation energy greater than 30 kcal/mol (corresponding to −7.5 kcal/mol relative to the native sequence, dashed line) were locally energy minimized to generate the red trajectory. Sequence 8871 is the top sequence when ranked by mean field dissociation energy (corresponding to Table 1b), and sequence 8888 is the top sequence when ranked by minimized dissociation energy (corresponding to Table 1d). The native sequence was found out of a possible 2×10<sup>12</sup> sequences after 8964 sequence evaluations. Dissociation and unfolding energies are reported in kcal/mol, relative to the native sequence. The number of protein-ligand hydrogen bonds was determined using bndlst. Shape complementarity (which ranges from 0 for perfectly non-complementary surfaces to 1 for perfectly complementary surfaces) was calculated using sc. Backbone coordinates for the bound state are from 2DRI, and backbone coordinates for the unbound state are from 1URP.</div> </figcaption> </figure> </div> <div class="see-all actions-bar"> <button class="show-more" aria-controls="slides-container" data-ga-category="figure" data-ga-action="show_all"> All figures (7) </button> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button>   <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption">  </button> </div> </div> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/19019243/" ref="article_id=19019243&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="19019243" data-ga-label=""> Ligand-induced conformational changes in a thermophilic ribose-binding protein. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Cuneo MJ, Beese LS, Hellinga HW.</span> <span class="docsum-authors short-authors">Cuneo MJ, et al.</span> <span class="docsum-journal-citation full-journal-citation">BMC Struct Biol. 2008 Nov 19;8:50. doi: 10.1186/1472-6807-8-50.</span> <span class="docsum-journal-citation short-journal-citation">BMC Struct Biol. 2008.</span> <span class="citation-part">PMID: <span class="docsum-pmid">19019243</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/33957147/" ref="article_id=33957147&linksrc=similar_articles_link&ordinalpos=2" data-ga-category="similar_article" data-ga-action="33957147" data-ga-label=""> Stability of Ligand-induced Protein Conformation Influences Affinity in Maltose-binding Protein. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">van den Noort M, de Boer M, Poolman B.</span> <span class="docsum-authors short-authors">van den Noort M, et al.</span> <span class="docsum-journal-citation full-journal-citation">J Mol Biol. 2021 Jul 23;433(15):167036. doi: 10.1016/j.jmb.2021.167036. Epub 2021 May 4.</span> <span class="docsum-journal-citation short-journal-citation">J Mol Biol. 2021.</span> <span class="citation-part">PMID: <span class="docsum-pmid">33957147</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/17242374/" ref="article_id=17242374&linksrc=similar_articles_link&ordinalpos=3" data-ga-category="similar_article" data-ga-action="17242374" data-ga-label=""> Analysis of ligand binding to a ribose biosensor using site-directed mutagenesis and fluorescence spectroscopy. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Vercillo NC, Herald KJ, Fox JM, Der BS, Dattelbaum JD.</span> <span class="docsum-authors short-authors">Vercillo NC, et al.</span> <span class="docsum-journal-citation full-journal-citation">Protein Sci. 2007 Mar;16(3):362-8. doi: 10.1110/ps.062595707. Epub 2007 Jan 22.</span> <span class="docsum-journal-citation short-journal-citation">Protein Sci. 2007.</span> <span class="citation-part">PMID: <span class="docsum-pmid">17242374</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/15111107/" ref="article_id=15111107&linksrc=similar_articles_link&ordinalpos=4" data-ga-category="similar_article" data-ga-action="15111107" data-ga-label=""> ABC transporter architecture and mechanism: implications from the crystal structures of BtuCD and BtuF. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Locher KP, Borths E.</span> <span class="docsum-authors short-authors">Locher KP, et al.</span> <span class="docsum-journal-citation full-journal-citation">FEBS Lett. 2004 Apr 30;564(3):264-8. doi: 10.1016/S0014-5793(04)00289-3.</span> <span class="docsum-journal-citation short-journal-citation">FEBS Lett. 2004.</span> <span class="citation-part">PMID: <span class="docsum-pmid">15111107</span></span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/15313245/" ref="article_id=15313245&linksrc=similar_articles_link&ordinalpos=5" data-ga-category="similar_article" data-ga-action="15313245" data-ga-label=""> Periplasmic binding proteins: a versatile superfamily for protein engineering. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Dwyer MA, Hellinga HW.</span> <span class="docsum-authors short-authors">Dwyer MA, et al.</span> <span class="docsum-journal-citation full-journal-citation">Curr Opin Struct Biol. 2004 Aug;14(4):495-504. doi: 10.1016/j.sbi.2004.07.004.</span> <span class="docsum-journal-citation short-journal-citation">Curr Opin Struct Biol. 2004.</span> <span class="citation-part">PMID: <span class="docsum-pmid">15313245</span></span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> </ul> <div class="actions-bar"> <a class="show-all-linked-articles" data-href="/?linkname=pubmed_pubmed&from_uid=18514737" data-ga-category="similar_article" data-ga-action="show_all" > See all similar articles </a> </div> </div> <div class="citedby-articles" id="citedby"> <h2 class="title"> Cited by </h2> <ul class="articles-list" id="citedby-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/34368100/" ref="article_id=34368100&linksrc=citedby_articles_link&ordinalpos=1" data-ga-category="cited_by" data-ga-action="34368100" data-ga-label=""> Ribose-Binding Protein Mutants With Improved Interaction Towards the Non-natural Ligand 1,3-Cyclohexanediol. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Tavares D, van der Meer JR.</span> <span class="docsum-authors short-authors">Tavares D, et al.</span> <span class="docsum-journal-citation full-journal-citation">Front Bioeng Biotechnol. 2021 Jul 23;9:705534. doi: 10.3389/fbioe.2021.705534. eCollection 2021.</span> <span class="docsum-journal-citation short-journal-citation">Front Bioeng Biotechnol. 2021.</span> <span class="citation-part">PMID: <span class="docsum-pmid">34368100</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/31851497/" ref="article_id=31851497&linksrc=citedby_articles_link&ordinalpos=2" data-ga-category="cited_by" data-ga-action="31851497" data-ga-label=""> Toward the Accuracy and Speed of Protein Side-Chain Packing: A Systematic Study on Rotamer Libraries. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Huang X, Pearce R, Zhang Y.</span> <span class="docsum-authors short-authors">Huang X, et al.</span> <span class="docsum-journal-citation full-journal-citation">J Chem Inf Model. 2020 Jan 27;60(1):410-420. doi: 10.1021/acs.jcim.9b00812. Epub 2019 Dec 31.</span> <span class="docsum-journal-citation short-journal-citation">J Chem Inf Model. 2020.</span> <span class="citation-part">PMID: <span class="docsum-pmid">31851497</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/31729460/" ref="article_id=31729460&linksrc=citedby_articles_link&ordinalpos=3" data-ga-category="cited_by" data-ga-action="31729460" data-ga-label=""> Computational redesign of the Escherichia coli ribose-binding protein ligand binding pocket for 1,3-cyclohexanediol and cyclohexanol. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Tavares D, Reimer A, Roy S, Joublin A, Sentchilo V, van der Meer JR.</span> <span class="docsum-authors short-authors">Tavares D, et al.</span> <span class="docsum-journal-citation full-journal-citation">Sci Rep. 2019 Nov 15;9(1):16940. doi: 10.1038/s41598-019-53507-5.</span> <span class="docsum-journal-citation short-journal-citation">Sci Rep. 2019.</span> <span class="citation-part">PMID: <span class="docsum-pmid">31729460</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/28604768/" ref="article_id=28604768&linksrc=citedby_articles_link&ordinalpos=4" data-ga-category="cited_by" data-ga-action="28604768" data-ga-label=""> Rosetta:MSF: a modular framework for multi-state computational protein design. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Löffler P, Schmitz S, Hupfeld E, Sterner R, Merkl R.</span> <span class="docsum-authors short-authors">Löffler P, et al.</span> <span class="docsum-journal-citation full-journal-citation">PLoS Comput Biol. 2017 Jun 12;13(6):e1005600. doi: 10.1371/journal.pcbi.1005600. eCollection 2017 Jun.</span> <span class="docsum-journal-citation short-journal-citation">PLoS Comput Biol. 2017.</span> <span class="citation-part">PMID: <span class="docsum-pmid">28604768</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/28287617/" ref="article_id=28287617&linksrc=citedby_articles_link&ordinalpos=5" data-ga-category="cited_by" data-ga-action="28287617" data-ga-label=""> Small Molecule-Induced Domain Swapping as a Mechanism for Controlling Protein Function and Assembly. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Karchin JM, Ha JH, Namitz KE, Cosgrove MS, Loh SN.</span> <span class="docsum-authors short-authors">Karchin JM, et al.</span> <span class="docsum-journal-citation full-journal-citation">Sci Rep. 2017 Mar 13;7:44388. doi: 10.1038/srep44388.</span> <span class="docsum-journal-citation short-journal-citation">Sci Rep. 2017.</span> <span class="citation-part">PMID: <span class="docsum-pmid">28287617</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> </ul> <div class="actions-bar"> <a class="show-all-linked-articles" data-href="/?linkname=pubmed_pubmed_citedin&from_uid=18514737" data-ga-category="cited_by" data-ga-action="show_all" > See all "Cited by" articles </a> </div> </div> <div class="references" id="references"> <h2 class="title"> References </h2> <div id='top-references-list' class="references-lists-container"> <div class="refs-list"> <ol id="top-references-list-1" class="references-list"> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Snow CD, Sorin EJ, Rhee YM, Pande VS. How well can simulation predict protein folding kinetics and thermodynamics? Annu. Rev. Biophys. Biomol. Struct. 2005;34:43–69. - <a class="reference-link" href="/15869383/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="15869383" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Ren PY, Ponder JW. Consistent treatment of inter- and intramolecular polarization in molecular mechanics calculations. J. Comput. Chem. 2002;23:1497–1506. - <a class="reference-link" href="/12395419/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="12395419" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Friesner RA. Modeling polarization in proteins and protein-ligand complexes: Methods and preliminary results. Adv. Protein Chem. 2006;72:79–104. - <a class="reference-link" href="/16581373/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="16581373" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Maple JR, Cao YX, Damm WG, Halgren TA, Kaminski GA, Zhang LY, Friesner RA. A polarizable force field and continuum solvation methodology for modeling of protein-ligand interactions. Journal of Chemical Theory and Computation. 2005;1:694–715. - <a class="reference-link" href="/26641692/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="26641692" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Mackerell AD., Jr Empirical force fields for biological macromolecules: overview and issues. J. Comput. Chem. 2004;25:1584–1604. - <a class="reference-link" href="/15264253/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="15264253" > PubMed </a> </li> </ol> </li> </ol> <div class="actions-bar"> <button class="show-all" ref="linksrc=show_all_references_link" aria-controls="top-references-list-1" data-next-page-url="/18514737/references/" data-ga-category="reference" data-ga-action="show_more" > Show all 55 references </button> </div> </div> </div> </div> <div id="publication-types" class="publication-types keywords-section"> <h2 class="title"> Publication types </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Research Support, N.I.H., Extramural" tabindex="0" aria-controls="keyword-actions-publication-types-0" aria-expanded="false" data-pinger-ignore> Research Support, N.I.H., Extramural </button><div id="keyword-actions-publication-types-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Research Support, N.I.H., Extramural"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Research+Support%2C+N.I.H.%2C+Extramural%22%5Bpt%5D&sort=date&sort_order=desc" data-href="/?term=%22Research+Support%2C+N.I.H.%2C+Extramural%22%5Bpt%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Research Support, N.I.H., Extramural"[pt]" data-ga-category="search" data-ga-action="pub_type" data-ga-label="Research Support, N.I.H., Extramural"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Research+Support%2C+N.I.H.%2C+Extramural" data-ga-category="search_mesh" data-ga-action="pub_type_link" data-ga-label="Research Support, N.I.H., Extramural"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Research Support, N.I.H., Extramural"[pt]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Research Support, N.I.H., Extramural"[pt]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="mesh-terms" class="mesh-terms keywords-section"> <h2 class="title"> MeSH terms </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Algorithms" tabindex="0" aria-controls="keyword-actions-mesh-terms-0" aria-expanded="false" data-pinger-ignore> Algorithms </button><div id="keyword-actions-mesh-terms-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Algorithms"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Algorithms%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Algorithms%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Algorithms"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Algorithms"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Algorithms" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Algorithms"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Algorithms"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Algorithms"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Amino Acid Sequence" tabindex="0" aria-controls="keyword-actions-mesh-terms-1" aria-expanded="false" data-pinger-ignore> Amino Acid Sequence </button><div id="keyword-actions-mesh-terms-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Amino Acid Sequence"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Amino+Acid+Sequence%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Amino+Acid+Sequence%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Amino Acid Sequence"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Amino Acid Sequence"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Amino+Acid+Sequence" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Amino Acid Sequence"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Amino Acid Sequence"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Amino Acid Sequence"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Binding Sites" tabindex="0" aria-controls="keyword-actions-mesh-terms-2" aria-expanded="false" data-pinger-ignore> Binding Sites </button><div id="keyword-actions-mesh-terms-2" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Binding Sites"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Binding+Sites%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Binding+Sites%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Binding Sites"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Binding Sites"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Binding+Sites" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Binding Sites"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Binding Sites"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Binding Sites"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Computer Simulation" tabindex="0" aria-controls="keyword-actions-mesh-terms-3" aria-expanded="false" data-pinger-ignore> Computer Simulation </button><div id="keyword-actions-mesh-terms-3" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Computer Simulation"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Computer+Simulation%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Computer+Simulation%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Computer Simulation"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Computer Simulation"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Computer+Simulation" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Computer Simulation"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Computer Simulation"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Computer Simulation"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Crystallography, X-Ray" tabindex="0" aria-controls="keyword-actions-mesh-terms-4" aria-expanded="false" data-pinger-ignore> Crystallography, X-Ray </button><div id="keyword-actions-mesh-terms-4" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Crystallography, X-Ray"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Crystallography%2C+X-Ray%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Crystallography%2C+X-Ray%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Crystallography, X-Ray"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Crystallography, X-Ray"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Crystallography%2C+X-Ray" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Crystallography, X-Ray"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Crystallography, X-Ray"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Crystallography, X-Ray"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Escherichia coli Proteins / chemistry*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-5" aria-expanded="false" data-pinger-ignore> Escherichia coli Proteins / chemistry* </button><div id="keyword-actions-mesh-terms-major-5" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Escherichia coli Proteins / chemistry*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Escherichia+coli+Proteins%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Escherichia+coli+Proteins%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Escherichia coli Proteins/chemistry"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Escherichia coli Proteins / chemistry*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Escherichia+coli+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Escherichia coli Proteins / chemistry*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Escherichia coli Proteins/chemistry"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Escherichia coli Proteins/chemistry"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Escherichia coli Proteins / genetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-6" aria-expanded="false" data-pinger-ignore> Escherichia coli Proteins / genetics </button><div id="keyword-actions-mesh-terms-6" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Escherichia coli Proteins / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Escherichia+coli+Proteins%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Escherichia+coli+Proteins%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Escherichia coli Proteins/genetics"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Escherichia coli Proteins / genetics"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Escherichia+coli+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Escherichia coli Proteins / genetics"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Escherichia coli Proteins/genetics"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Escherichia coli Proteins/genetics"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Escherichia coli Proteins / metabolism*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-7" aria-expanded="false" data-pinger-ignore> Escherichia coli Proteins / metabolism* </button><div id="keyword-actions-mesh-terms-major-7" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Escherichia coli Proteins / metabolism*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Escherichia+coli+Proteins%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Escherichia+coli+Proteins%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Escherichia coli Proteins/metabolism"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Escherichia coli Proteins / metabolism*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Escherichia+coli+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Escherichia coli Proteins / metabolism*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Escherichia coli Proteins/metabolism"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Escherichia coli Proteins/metabolism"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Ligands*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-8" aria-expanded="false" data-pinger-ignore> Ligands* </button><div id="keyword-actions-mesh-terms-major-8" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Ligands*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Ligands%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Ligands%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Ligands"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Ligands*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Ligands" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Ligands*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Ligands"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Ligands"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Models, Biological*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-9" aria-expanded="false" data-pinger-ignore> Models, Biological* </button><div id="keyword-actions-mesh-terms-major-9" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Models, Biological*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Models%2C+Biological%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Models%2C+Biological%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Models, Biological"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Models, Biological*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Models%2C+Biological" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Models, Biological*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Models, Biological"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Models, Biological"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Molecular Sequence Data" tabindex="0" aria-controls="keyword-actions-mesh-terms-10" aria-expanded="false" data-pinger-ignore> Molecular Sequence Data </button><div id="keyword-actions-mesh-terms-10" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Molecular Sequence Data"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Molecular+Sequence+Data%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Molecular+Sequence+Data%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Molecular Sequence Data"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Molecular Sequence Data"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Molecular+Sequence+Data" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Molecular Sequence Data"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Molecular Sequence Data"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Molecular Sequence Data"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Molecular Structure" tabindex="0" aria-controls="keyword-actions-mesh-terms-11" aria-expanded="false" data-pinger-ignore> Molecular Structure </button><div id="keyword-actions-mesh-terms-11" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Molecular Structure"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Molecular+Structure%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Molecular+Structure%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Molecular Structure"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Molecular Structure"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Molecular+Structure" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Molecular Structure"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Molecular Structure"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Molecular Structure"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Periplasmic Binding Proteins / chemistry*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-12" aria-expanded="false" data-pinger-ignore> Periplasmic Binding Proteins / chemistry* </button><div id="keyword-actions-mesh-terms-major-12" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Periplasmic Binding Proteins / chemistry*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Periplasmic+Binding+Proteins%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Periplasmic+Binding+Proteins%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Periplasmic Binding Proteins/chemistry"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Periplasmic Binding Proteins / chemistry*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Periplasmic+Binding+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Periplasmic Binding Proteins / chemistry*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Periplasmic Binding Proteins/chemistry"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Periplasmic Binding Proteins/chemistry"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Periplasmic Binding Proteins / genetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-13" aria-expanded="false" data-pinger-ignore> Periplasmic Binding Proteins / genetics </button><div id="keyword-actions-mesh-terms-13" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Periplasmic Binding Proteins / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Periplasmic+Binding+Proteins%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Periplasmic+Binding+Proteins%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Periplasmic Binding Proteins/genetics"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Periplasmic Binding Proteins / genetics"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Periplasmic+Binding+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Periplasmic Binding Proteins / genetics"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Periplasmic Binding Proteins/genetics"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Periplasmic Binding Proteins/genetics"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Periplasmic Binding Proteins / metabolism*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-14" aria-expanded="false" data-pinger-ignore> Periplasmic Binding Proteins / metabolism* </button><div id="keyword-actions-mesh-terms-major-14" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Periplasmic Binding Proteins / metabolism*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Periplasmic+Binding+Proteins%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Periplasmic+Binding+Proteins%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Periplasmic Binding Proteins/metabolism"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Periplasmic Binding Proteins / metabolism*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Periplasmic+Binding+Proteins" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Periplasmic Binding Proteins / metabolism*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Periplasmic Binding Proteins/metabolism"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Periplasmic Binding Proteins/metabolism"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Protein Binding" tabindex="0" aria-controls="keyword-actions-mesh-terms-15" aria-expanded="false" data-pinger-ignore> Protein Binding </button><div id="keyword-actions-mesh-terms-15" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Protein Binding"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Protein+Binding%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Protein+Binding%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Protein Binding"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Protein Binding"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Protein+Binding" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Protein Binding"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Protein Binding"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Protein Binding"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Protein Conformation" tabindex="0" aria-controls="keyword-actions-mesh-terms-16" aria-expanded="false" data-pinger-ignore> Protein Conformation </button><div id="keyword-actions-mesh-terms-16" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Protein Conformation"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Protein+Conformation%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Protein+Conformation%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Protein Conformation"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Protein Conformation"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Protein+Conformation" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Protein Conformation"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Protein Conformation"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Protein Conformation"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Protein Interaction Mapping*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-17" aria-expanded="false" data-pinger-ignore> Protein Interaction Mapping* </button><div id="keyword-actions-mesh-terms-major-17" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Protein Interaction Mapping*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Protein+Interaction+Mapping%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Protein+Interaction+Mapping%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Protein Interaction Mapping"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Protein Interaction Mapping*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Protein+Interaction+Mapping" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Protein Interaction Mapping*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Protein Interaction Mapping"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Protein Interaction Mapping"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="substances" class="substances keywords-section"> <h2 class="title"> Substances </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Escherichia coli Proteins" tabindex="0" aria-controls="keyword-actions-substances-0" aria-expanded="false" data-pinger-ignore> Escherichia coli Proteins </button><div id="keyword-actions-substances-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Escherichia coli Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Escherichia+coli+Proteins%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Escherichia+coli+Proteins%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Escherichia coli Proteins"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Escherichia coli Proteins"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Escherichia+coli+Proteins%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Escherichia coli Proteins"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Escherichia coli Proteins"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Escherichia coli Proteins"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Ligands" tabindex="0" aria-controls="keyword-actions-substances-1" aria-expanded="false" data-pinger-ignore> Ligands </button><div id="keyword-actions-substances-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Ligands"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Ligands%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Ligands%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Ligands"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Ligands"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Ligands%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Ligands"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Ligands"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Ligands"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Periplasmic Binding Proteins" tabindex="0" aria-controls="keyword-actions-substances-2" aria-expanded="false" data-pinger-ignore> Periplasmic Binding Proteins </button><div id="keyword-actions-substances-2" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Periplasmic Binding Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Periplasmic+Binding+Proteins%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Periplasmic+Binding+Proteins%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Periplasmic Binding Proteins"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Periplasmic Binding Proteins"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Periplasmic+Binding+Proteins%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Periplasmic Binding Proteins"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Periplasmic Binding Proteins"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Periplasmic Binding Proteins"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RbsB protein, E coli" tabindex="0" aria-controls="keyword-actions-substances-3" aria-expanded="false" data-pinger-ignore> RbsB protein, E coli </button><div id="keyword-actions-substances-3" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RbsB protein, E coli"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RbsB+protein%2C+E+coli%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22RbsB+protein%2C+E+coli%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="RbsB protein, E coli"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="RbsB protein, E coli"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22RbsB+protein%2C+E+coli%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="RbsB protein, E coli"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RbsB protein, E coli"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RbsB protein, E coli"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="related-links" class="related-links"> <h2 class="title"> Related information </h2> <ul class="related-links-list"><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=18514737" ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=18514737&ordinalpos=1&linkpos=1"> MedGen </a></li></ul> </div> <div id="grants" class="grants"> <h2 class="title"> Grants and funding </h2> <div class="grants-list"><ul id="grants-head-list"><li class="grant-item"><a title="All articles for grant DP1 OD000429-03/OD/NIH HHS/United States" href="/?term=DP1+OD000429-03%2FOD%2FNIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="DP1 OD000429-03" > DP1 OD000429-03/OD/NIH HHS/United States </a></li><li class="grant-item"><a title="All articles for grant T32 GM007365/GM/NIGMS NIH HHS/United States" href="/?term=T32+GM007365%2FGM%2FNIGMS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="T32 GM007365" > T32 GM007365/GM/NIGMS NIH HHS/United States </a></li><li class="grant-item"><a title="All articles for grant 1-DP1-0D000429/DP/NCCDPHP CDC HHS/United States" href="/?term=1-DP1-0D000429%2FDP%2FNCCDPHP+CDC+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="1-DP1-0D000429" > 1-DP1-0D000429/DP/NCCDPHP CDC HHS/United States </a></li><li class="grant-item"><a title="All articles for grant R01 GM068126/GM/NIGMS NIH HHS/United States" href="/?term=R01+GM068126%2FGM%2FNIGMS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="R01 GM068126" > R01 GM068126/GM/NIGMS NIH HHS/United States </a></li><li class="grant-item"><a title="All articles for grant DP1 OD000429-02/OD/NIH HHS/United States" href="/?term=DP1+OD000429-02%2FOD%2FNIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="DP1 OD000429-02" > DP1 OD000429-02/OD/NIH HHS/United States </a></li></ul><ul id="grants-tail-list" class="list-tail"><li class="grant-item"><a title="All articles for grant DP1 OD000429/OD/NIH HHS/United States" href="/?term=DP1+OD000429%2FOD%2FNIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="DP1 OD000429" > DP1 OD000429/OD/NIH HHS/United States </a></li><li class="grant-item"><a title="All articles for grant DP1 OD000429-01/OD/NIH HHS/United States" href="/?term=DP1+OD000429-01%2FOD%2FNIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="DP1 OD000429-01" > DP1 OD000429-01/OD/NIH HHS/United States </a></li><li class="grant-item"><a title="All articles for grant GM068126-01/GM/NIGMS NIH HHS/United States" href="/?term=GM068126-01%2FGM%2FNIGMS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="GM068126-01" > GM068126-01/GM/NIGMS NIH HHS/United States </a></li><li class="grant-item"><a title="All articles for grant 5T32 GM07365-28/GM/NIGMS NIH HHS/United States" href="/?term=5T32+GM07365-28%2FGM%2FNIGMS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc" ref="linksrc=grant_link" data-ga-category="search" data-ga-action="grant" data-ga-label="5T32 GM07365-28" > 5T32 GM07365-28/GM/NIGMS NIH HHS/United States </a></li></ul></div><div class="actions-bar"><button class="show-all" ref="linksrc=show_all_grants_link" aria-controls="grants-tail-list" title="Show all grants" data-ga-category="grant" data-ga-action="show_more" > Show all 9 grants </button></div> </div> <div id="linkout" class="linkout"> <h2 class="title"> LinkOut - more resources </h2> <ul class="linkout-list"><li><h3 class="linkout-category">Full Text Sources</h3><ul class="linkout-category-links"><li><a href="https://linkinghub.elsevier.com/retrieve/pii/S0022-2836(08)00408-7" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=3048&uid=18514737&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=2985088R" data-ga-category="link_out" data-ga-action="Full Text Sources" data-ga-label="Elsevier Science" > Elsevier Science </a></li><li><a href="https://europepmc.org/abstract/MED/18514737" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=6082&uid=18514737&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=2985088R" data-ga-category="link_out" data-ga-action="Full Text Sources" data-ga-label="Europe PubMed Central" > Europe PubMed Central </a></li><li><a href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/18514737/" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=3494&uid=18514737&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=2985088R" data-ga-category="link_out" data-ga-action="Full Text Sources" data-ga-label="PubMed Central" > PubMed Central </a></li></ul></li></ul> </div> </main> <div class="overlay" role="dialog" aria-label="Full Text Links Dialog"> <div id="full-text-links-dialog" class="dialog full-text-links-dialog"> <strong class="title">Full text links</strong> <button class="close-overlay" tabindex="3">[x]</button> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://linkinghub.elsevier.com/retrieve/pii/S0022-2836(08)00408-7" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=18514737&db=pubmed&nlmid=2985088R" title="See full text options at Elsevier Science" tabindex="1" data-ga-category="full_text" data-ga-action="Elsevier Science" data-ga-label="18514737" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="full text provider logo"><span class="text"> Elsevier Science </span></a><a class="link-item pmc " href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/18514737/" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=18514737&db=pubmed&nlmid=2985088R" title="Free full text at PubMed Central" tabindex="2" data-ga-category="full_text" data-ga-action="PMC" data-ga-label="18514737" ><span class="text"> Free PMC article </span></a> </div> </div> </div> <div class="overlay" role="dialog" aria-label="Citation Dialog"> <div class="dialog citation-dialog"> <button class="close-overlay" tabindex="1">[x]</button> <div class="title">Cite</div> <div class="citation-text-block"> <div class="citation-text"></div> <div class="citation-actions"> <button class="copy-button dialog-focus" data-ga-category="save_share" data-ga-action="cite" data-ga-label="copy" tabindex="2"> Copy </button> <form method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="qRScoDTzUHFQDnNF6LITARirwwkFsEVcIP0PJtUqegNK5YKxgcSTnl6VaYS9yzjt"> <button type="submit" class="export-button" data-ga-category="save_share" data-ga-action="cite" data-ga-label="download" title="Download a file for external citation management software" tabindex="3"> <span class="download-title">Download .nbib</span> <span class="download-title-mobile">.nbib</span> </button> </form> <div class="citation-style-selector-wrapper"> <label class="selector-label">Format:</label> <select aria-label="Format" class="citation-style-selector" tabindex="4"> <option data-style-url-name="ama" value="AMA" > AMA </option> <option data-style-url-name="apa" value="APA" > APA </option> <option data-style-url-name="mla" value="MLA" > MLA </option> <option data-style-url-name="nlm" value="NLM" selected="selected"> NLM </option> </select> </div> </div> </div> </div> </div> <div class="overlay" role="dialog" aria-label="More Actions Dialog"> <div id="more-actions-dialog" class="dialog more-actions-dialog"> <strong class="title">Send To</strong> <ul class="more-actions-links"> <li><a id="clipboard-trigger" role="button" class="submit-button clipboard-trigger clipboard-trigger-target dialog-focus link-item " href="#">Clipboard</a></li> <li><a class="email-trigger link-item" role="button" href="#">Email</a></li> <li><a class="save-trigger link-item" role="button" href="#">Save</a></li> <li><a class="link-item" role="button" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18514737%2F%23open-bibliography-panel">My Bibliography</a></li> <li><a class="link-item" role="button" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18514737%2F%23open-collections-panel">Collections</a></li> <li><a class="citation-manager-trigger link-item" role="button" href="#">Citation Manager</a></li> </ul> <button class="close-overlay">[x]</button> </div> </div> </div> <div id="ncbi-footer"> <div class="literature-footer" role="complementary" title="Links to NCBI Literature Resources"> <div class="usa-grid"> <p class="literature-footer-text">NCBI Literature Resources</p> <p class="literature-footer-text"> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh/">MeSH</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="pmc_link" href="https://www.ncbi.nlm.nih.gov/pmc/">PMC</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="bookshelf_link" href="https://www.ncbi.nlm.nih.gov/books">Bookshelf</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="disclaimer_link" href="/disclaimer/">Disclaimer</a> </p> <p class="literature-footer-text attribution-statement">The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.</p> </div> </div>  <footer> <section class="icon-section"> <div id="icon-section-header" class="icon-section_header">Follow NCBI</div> <div class="grid-container container"> <div class="icon-section_container"> <a class="footer-icon" id="footer_twitter" href="https://twitter.com/ncbi" aria-label="Twitter"> <svg width="40" height="40" viewBox="0 0 40 37" fill="none" xmlns="http://www.w3.org/2000/svg"> <title>Twitter</title> <g id="twitterx1008"> <path id="path1008" d="M6.06736 7L16.8778 20.8991L6.00001 32.2H10.2L18.6 23.1L25.668 32.2H34L22.8 17.5L31.9 7H28.4L20.7 15.4L14.401 7H6.06898H6.06736ZM9.66753 8.73423H12.9327L29.7327 30.4658H26.5697L9.66753 8.73423Z" fill="#5B616B"/> </g> </svg> </a> <a class="footer-icon" id="footer_facebook" href="https://www.facebook.com/ncbi.nlm" aria-label="Facebook"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <title>Facebook</title> <path class="cls-11" d="M210.5,115.12H171.74V97.82c0-8.14,5.39-10,9.19-10h27.14V52l-39.32-.12c-35.66,0-42.42,26.68-42.42,43.77v19.48H99.09v36.32h27.24v109h45.41v-109h35Z"> </path> </svg></a> <a class="footer-icon" id="footer_linkedin" href="https://www.linkedin.com/company/ncbinlm" aria-label="LinkedIn"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <title>LinkedIn</title> <path class="cls-11" d="M101.64,243.37H57.79v-114h43.85Zm-22-131.54h-.26c-13.25,0-21.82-10.36-21.82-21.76,0-11.65,8.84-21.15,22.33-21.15S101.7,78.72,102,90.38C102,101.77,93.4,111.83,79.63,111.83Zm100.93,52.61A17.54,17.54,0,0,0,163,182v61.39H119.18s.51-105.23,0-114H163v13a54.33,54.33,0,0,1,34.54-12.66c26,0,44.39,18.8,44.39,55.29v58.35H198.1V182A17.54,17.54,0,0,0,180.56,164.44Z"> </path> </svg></a> <a class="footer-icon" id="footer_github" href="https://github.com/ncbi" aria-label="GitHub"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <defs> <style> .cls-11, .cls-12 { fill: #737373; } .cls-11 { fill-rule: evenodd; } </style> </defs> <title>GitHub</title> <path class="cls-11" d="M151.36,47.28a105.76,105.76,0,0,0-33.43,206.1c5.28,1,7.22-2.3,7.22-5.09,0-2.52-.09-10.85-.14-19.69-29.42,6.4-35.63-12.48-35.63-12.48-4.81-12.22-11.74-15.47-11.74-15.47-9.59-6.56.73-6.43.73-6.43,10.61.75,16.21,10.9,16.21,10.9,9.43,16.17,24.73,11.49,30.77,8.79,1-6.83,3.69-11.5,6.71-14.14C108.57,197.1,83.88,188,83.88,147.51a40.92,40.92,0,0,1,10.9-28.39c-1.1-2.66-4.72-13.42,1-28,0,0,8.88-2.84,29.09,10.84a100.26,100.26,0,0,1,53,0C198,88.3,206.9,91.14,206.9,91.14c5.76,14.56,2.14,25.32,1,28a40.87,40.87,0,0,1,10.89,28.39c0,40.62-24.74,49.56-48.29,52.18,3.79,3.28,7.17,9.71,7.17,19.58,0,14.15-.12,25.54-.12,29,0,2.82,1.9,6.11,7.26,5.07A105.76,105.76,0,0,0,151.36,47.28Z"> </path> <path class="cls-12" d="M85.66,199.12c-.23.52-1.06.68-1.81.32s-1.2-1.06-.95-1.59,1.06-.69,1.82-.33,1.21,1.07.94,1.6Zm-1.3-1"> </path> <path class="cls-12" d="M90,203.89c-.51.47-1.49.25-2.16-.49a1.61,1.61,0,0,1-.31-2.19c.52-.47,1.47-.25,2.17.49s.82,1.72.3,2.19Zm-1-1.08"> </path> <path class="cls-12" d="M94.12,210c-.65.46-1.71,0-2.37-.91s-.64-2.07,0-2.52,1.7,0,2.36.89.65,2.08,0,2.54Zm0,0"></path> <path class="cls-12" d="M99.83,215.87c-.58.64-1.82.47-2.72-.41s-1.18-2.06-.6-2.7,1.83-.46,2.74.41,1.2,2.07.58,2.7Zm0,0"> </path> <path class="cls-12" d="M107.71,219.29c-.26.82-1.45,1.2-2.64.85s-2-1.34-1.74-2.17,1.44-1.23,2.65-.85,2,1.32,1.73,2.17Zm0,0"> </path> <path class="cls-12" d="M116.36,219.92c0,.87-1,1.59-2.24,1.61s-2.29-.68-2.3-1.54,1-1.59,2.26-1.61,2.28.67,2.28,1.54Zm0,0"> </path> <path class="cls-12" d="M124.42,218.55c.15.85-.73,1.72-2,1.95s-2.37-.3-2.52-1.14.73-1.75,2-2,2.37.29,2.53,1.16Zm0,0"></path> </svg></a> <a class="footer-icon" id="footer_blog" href="https://ncbiinsights.ncbi.nlm.nih.gov/" aria-label="Blog"> <svg id="Layer_1" data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 40"><defs><style>.cls-1{fill:#737373;}</style></defs><path class="cls-1" d="M14,30a4,4,0,1,1-4-4,4,4,0,0,1,4,4Zm11,3A19,19,0,0,0,7.05,15a1,1,0,0,0-1,1v3a1,1,0,0,0,.93,1A14,14,0,0,1,20,33.07,1,1,0,0,0,21,34h3a1,1,0,0,0,1-1Zm9,0A28,28,0,0,0,7,6,1,1,0,0,0,6,7v3a1,1,0,0,0,1,1A23,23,0,0,1,29,33a1,1,0,0,0,1,1h3A1,1,0,0,0,34,33Z"/></svg> </a> </div> </div> </section> <section class="container-fluid bg-primary"> <div class="container pt-5"> <div class="row mt-3"> <div class="col-lg-3 col-12"> <p><a class="text-white" href="https://www.nlm.nih.gov/socialmedia/index.html">Connect with NLM</a></p> <ul class="list-inline social_media"> <li class="list-inline-item"><a href="https://twitter.com/NLM_NIH" aria-label="Twitter" target="_blank" rel="noopener noreferrer"> <svg width="35" height="35" viewBox="0 0 38 35" fill="none" xmlns="http://www.w3.org/2000/svg"> <title>Twitter</title> <g id="twitterx1009" clip-path="url(#clip0_65276_3946)"> <path id="Vector" d="M17.5006 34.6565C26.9761 34.6565 34.6575 26.9751 34.6575 17.4996C34.6575 8.02416 26.9761 0.342773 17.5006 0.342773C8.02514 0.342773 0.34375 8.02416 0.34375 17.4996C0.34375 26.9751 8.02514 34.6565 17.5006 34.6565Z" fill="#205493" stroke="white" stroke-width="1.2" stroke-miterlimit="10"></path> <path id="path1009" d="M8.54811 8.5L16.2698 18.4279L8.50001 26.5H11.5L17.5 20L22.5486 26.5H28.5L20.5 16L27 8.5H24.5L19 14.5L14.5007 8.5H8.54927H8.54811ZM11.1197 9.73873H13.4519L25.4519 25.2613H23.1926L11.1197 9.73873Z" fill="white"></path> </g> <defs> <clipPath id="clip0_65276_3946"> <rect width="38" height="38" fill="white"></rect> </clipPath> </defs> </svg></a> </li> <li class="list-inline-item"><a href="https://www.facebook.com/nationallibraryofmedicine" aria-label="Facebook" rel="noopener noreferrer" target="_blank"> <svg version="1.1" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve"> <style type="text/css"> .st10 { fill: #FFFFFF; } .st110 { fill: none; stroke: #FFFFFF; stroke-width: 8; stroke-miterlimit: 10; } </style> <title>SM-Facebook</title> <g> <g> <path class="st10" d="M159,99.1h-24V88.4c0-5,3.3-6.2,5.7-6.2h16.8V60l-24.4-0.1c-22.1,0-26.2,16.5-26.2,27.1v12.1H90v22.5h16.9 v67.5H135v-67.5h21.7L159,99.1z"></path> </g> </g> <circle class="st110" cx="123.6" cy="123.2" r="108.2"></circle> </svg> </a></li> <li class="list-inline-item"><a href="https://www.youtube.com/user/NLMNIH" aria-label="Youtube" target="_blank" rel="noopener noreferrer"><svg version="1.1" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve"> <title>SM-Youtube</title> <style type="text/css"> .st4 { fill: none; stroke: #FFFFFF; stroke-width: 8; stroke-miterlimit: 10; } .st5 { fill: #FFFFFF; } </style> <circle class="st4" cx="124.2" cy="123.4" r="108.2"></circle> <g transform="translate(0,-952.36218)"> <path class="st5" d="M88.4,1037.4c-10.4,0-18.7,8.3-18.7,18.7v40.1c0,10.4,8.3,18.7,18.7,18.7h72.1c10.4,0,18.7-8.3,18.7-18.7 v-40.1c0-10.4-8.3-18.7-18.7-18.7H88.4z M115.2,1058.8l29.4,17.4l-29.4,17.4V1058.8z"></path> </g> </svg></a></li> </ul> </div> <div class="col-lg-3 col-12"> <p class="address_footer text-white">National Library of Medicine<br> <a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br> Bethesda, MD 20894</a></p> </div> <div class="col-lg-3 col-12 centered-lg"> <p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br> <a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br> <a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p> </div> <div class="col-lg-3 col-12 centered-lg"> <p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br> <a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br> <a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p> </div> </div> <div class="row"> <div class="col-lg-12 centered-lg"> <nav class="bottom-links"> <ul class="mt-3"> <li> <a class="text-white" href="//www.nlm.nih.gov/">NLM</a> </li> <li> <a class="text-white" href="https://www.nih.gov/">NIH</a> </li> <li> <a class="text-white" href="https://www.hhs.gov/">HHS</a> </li> <li> <a class="text-white" href="https://www.usa.gov/">USA.gov</a> </li> </ul> </nav> </div> </div> </div> </section> </footer>   <script type="text/javascript"> var nwds_version = "1.2.3"; var meta_nwds_ver = document.createElement('meta'); meta_nwds_ver.name = 'ncbi_nwds_ver'; meta_nwds_ver.content = nwds_version; document.getElementsByTagName('head')[0].appendChild(meta_nwds_ver); var meta_nwds = document.createElement('meta'); meta_nwds.name = 'ncbi_nwds'; meta_nwds.content = 'yes'; document.getElementsByTagName('head')[0].appendChild(meta_nwds); var alertsUrl = "/core/alerts/alerts.js"; if (typeof ncbiBaseUrl !== 'undefined') { alertsUrl = ncbiBaseUrl + alertsUrl; } </script> </div>  <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/js/output.293fbf76aa18.js"></script>  <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/js/output.550e9c8906a2.js"></script> <script> ncbi.awesome.basePage.init({ userInfo: { isLoggedIn: false, username: "", loginUrl: "https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F18514737%2F", logoutUrl: "https://www.ncbi.nlm.nih.gov/account/signout/?back_url=https%3A//pubmed.ncbi.nlm.nih.gov/18514737/" }, baseUrl: 'https://www.ncbi.nlm.nih.gov', noSessionCookieName: "pm-ns", searchIdCookieName: "pm-sid", adjNavSearchIdCookieName: "pm-adjnav-sid", searchFormSubmittedCookieName: "pm-sfs", isOnSearchPageCookieName: "pm-iosp", backToSearchCookieName: "pm-btsl", clinicalSeeAllCookieName: "pm-csa", jsCookieDomain: "pubmed.ncbi.nlm.nih.gov", userShareRequestFailed: "", noSharedSettings: "myncbi_no_shared_settings", noSharedAccount: "myncbi_no_shared_account" }); </script> <script type="module"> import dismissableNCBIAlert from "https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/core/dismissable-ncbi-alert.js"; jQuery.getScript("https://www.ncbi.nlm.nih.gov/core/alerts/alerts.js", function () { galert(['body > *:last-child']); dismissableNCBIAlert(); }).fail(function() { }); </script> <script defer type="text/javascript" src="https://cdn.ncbi.nlm.nih.gov/core/pinger/pinger.js"> </script> <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/js/output.04d45d85d031.js"></script> <script> ncbi.awesome.articlePage.init({ baseSuggestionsUrl: "/suggestions/", mathJaxUrl: "https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/mathjax/unpacked/MathJax.js?config=MML_CHTML", clipboardAPIRoot: "/ajax/clipboard/", clipboardNextPageUrl: "/clipboard-next-page/", searchIdCookieName: "pm-sid", searchFormSubmittedCookieName: "pm-sfs", backToSearchCookieName: "pm-btsl", jsCookieDomain: "pubmed.ncbi.nlm.nih.gov", longTermPrefix: "longquery", adjNavURLPath: "/18514737/adj-nav/", adjNavSearchIdCookieName: "pm-adjnav-sid", articlePageUrl: "/18514737/", markJSUrl: "https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/mark.js/dist/jquery.mark.js", termHighlightColor: "", highlightedTokens: "", citeFormatPreferenceCookieName: "pm-cf" }); </script> </body> </html>

CINXE.COM

Design of protein-ligand binding based on the molecular-mechanics energy model - PubMed