{"id":351,"date":"2020-06-09T11:18:16","date_gmt":"2020-06-09T11:18:16","guid":{"rendered":"https:\/\/www.embl.org\/groups\/chemical-biology\/?page_id=351"},"modified":"2021-09-09T11:31:26","modified_gmt":"2021-09-09T11:31:26","slug":"computational-chemistry","status":"publish","type":"page","link":"https:\/\/www.embl.org\/groups\/chemical-biology\/computational-chemistry\/","title":{"rendered":"Computational Chemistry"},"content":{"rendered":"\n<div class=\"vf-grid | vf-grid__col-3\"><div class=\"vf-grid__col--span-2\"><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<p>Computational chemistry methods are integral to the process of active molecule identification and optimisation. These include:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Chemoinformatics approaches<\/li><li>Molecular modelling<\/li><li>Computational screening using ligand-based and structure-based design strategies<\/li><li>Managing compound acquisition through our chemistry partners<\/li><li>Commercial software available: SYBYL-X including SurflexDock and SurflexSim, LeadIT including FlexX and FlexS, Muse, Spartan<\/li><li>Access to the HPC compute cluster at EMBL which provides access to more than 5800 CPUs for scientific computing at EMBL<\/li><\/ul>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<div class=\"vf-grid | vf-grid__col-1\"><div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<div class=\"vf-tabs\"><ul class=\"vf-tabs__list\" data-vf-js-tabs=\"true\"><li class=\"vf-tabs__item\"><a class=\"vf-tabs__link\" href=\"#vf-tabs__section-9e72028d-6b89-4c1f-968e-fc4707efa9fb\">Structural biology<\/a><\/li><li class=\"vf-tabs__item\"><a class=\"vf-tabs__link\" href=\"#vf-tabs__section-c28ce25f-57e8-4946-b0e2-eec63f8e3e7d\">Ligand-based design<\/a><\/li><li class=\"vf-tabs__item\"><a class=\"vf-tabs__link\" href=\"#vf-tabs__section-4ce406f5-1cf3-4318-8ff7-051ebc7a477b\">Receptor-based design<\/a><\/li><li class=\"vf-tabs__item\"><a class=\"vf-tabs__link\" href=\"#vf-tabs__section-8489137d-14dd-4a52-9f73-ea85197474dd\">Data analysis<\/a><\/li><li class=\"vf-tabs__item\"><a class=\"vf-tabs__link\" href=\"#vf-tabs__section-90de3259-335f-4a7f-b326-6decf64533f4\">Library design<\/a><\/li><li class=\"vf-tabs__item\"><a class=\"vf-tabs__link\" href=\"#vf-tabs__section-6fd98a15-07aa-4e0e-92ef-06809f90d615\">Compound acquisitions<\/a><\/li><\/ul><div class=\"vf-tabs-content\" data-vf-js-tabs-content=\"true\">\n<section class=\"vf-tabs__section\" id=\"vf-tabs__section-9e72028d-6b89-4c1f-968e-fc4707efa9fb\"><h2>Structural biology<\/h2>\n<div class=\"vf-grid | vf-grid__col-3\"><div class=\"vf-grid__col--span-2\"><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<ul class=\"wp-block-list\"><li>Protein structure visualisation (3D visualisation capabilities)<\/li><li>Binding site identification<\/li><li>Analysis of interaction profiles of ligands inside a binding site<\/li><li>Homology modeling; leveraging known protein structures to unknowns with similar sequence<\/li><\/ul>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<figure class=\"vf-figure wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"350\" height=\"250\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/structural-biology-1.jpg\" alt=\"\" class=\"wp-image-386\" srcset=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/structural-biology-1.jpg 350w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/structural-biology-1-300x214.jpg 300w\" sizes=\"auto, (max-width: 350px) 100vw, 350px\" \/><\/figure>\n\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n\n\n\n<section class=\"vf-tabs__section\" id=\"vf-tabs__section-c28ce25f-57e8-4946-b0e2-eec63f8e3e7d\"><h2>Ligand-based design<\/h2>\n<div class=\"vf-grid | vf-grid__col-3\"><div class=\"vf-grid__col--span-2\"><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<ul class=\"wp-block-list\"><li>Pharmacophore elucidation&nbsp;based on known active ligands<\/li><li>Database searching for new active compounds based on pharmacophore<\/li><li>Properties prediction based on models from data of known ligands<\/li><li>SAR, ADME predictions based on data from known ligands<\/li><\/ul>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<figure class=\"vf-figure wp-block-image size-large\"><a href=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/pharmacophore_l_820.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"820\" height=\"678\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/pharmacophore_l_820.jpg\" alt=\"Three MAP-kinase P38 inhibitors were analyzed and important features for binding detected. These are two hydrophobic groups (cyan spheres in the right part of the picture) plus a hydrogen bond accepting capability (green). This is found in all three compounds. Having an additional hydrophobic feature (cyan sphere in the centre of the picture) and another hydrogen bond accepting group at the magenta spot enhance affinity as the green and the purple molecule sharing these features have higher inhibitor activity.\" class=\"wp-image-394\" srcset=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/pharmacophore_l_820.jpg 820w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/pharmacophore_l_820-300x248.jpg 300w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/pharmacophore_l_820-768x635.jpg 768w\" sizes=\"auto, (max-width: 820px) 100vw, 820px\" \/><\/a><figcaption class=\"vf-figure__caption\">Three MAP-kinase P38 inhibitors were analyzed and important features for binding detected. These are two hydrophobic groups (cyan spheres in the right part of the picture) plus a hydrogen bond accepting capability (green). This is found in all three compounds. Having an additional hydrophobic feature (cyan sphere in the centre of the picture) and another hydrogen bond accepting group at the magenta spot enhance affinity as the green and the purple molecule sharing these features have higher inhibitor activity.<\/figcaption><\/figure>\n\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n\n\n\n<section class=\"vf-tabs__section\" id=\"vf-tabs__section-4ce406f5-1cf3-4318-8ff7-051ebc7a477b\"><h2>Receptor-based design<\/h2>\n<div class=\"vf-grid | vf-grid__col-3\"><div class=\"vf-grid__col--span-2\"><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<ul class=\"wp-block-list\"><li>Docking of ligands\u00a0into target structure<ul><li>Virtual screening; selection of compounds from large data set based on docking<\/li><li>Ligand refinement based on docked structure<\/li><\/ul><\/li><li><em>De novo<\/em>\u00a0design of ligands from protein structure; no lead compound; spatial arrangement of suitable binding groups<\/li><\/ul>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<figure class=\"vf-figure wp-block-image size-large\"><a href=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/docking-of-ligands_m.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"820\" height=\"691\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/docking-of-ligands_m.jpg\" alt=\"\" class=\"wp-image-393\" srcset=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/docking-of-ligands_m.jpg 820w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/docking-of-ligands_m-300x253.jpg 300w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/docking-of-ligands_m-768x647.jpg 768w\" sizes=\"auto, (max-width: 820px) 100vw, 820px\" \/><\/a><figcaption class=\"vf-figure__caption\">Docking of ligands<\/figcaption><\/figure>\n\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n\n\n\n<section class=\"vf-tabs__section\" id=\"vf-tabs__section-8489137d-14dd-4a52-9f73-ea85197474dd\"><h2>Data analysis<\/h2>\n<div class=\"vf-grid | vf-grid__col-3\"><div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<ul class=\"wp-block-list\"><li>Diversity and similarity tools<\/li><li>Library creation<ul><li>For random screening<\/li><li>For specific targets<\/li><li>Exploration of SAR (iterative)<\/li><\/ul><\/li><\/ul>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<figure class=\"vf-figure wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"350\" height=\"213\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/data-analysis-1.jpg\" alt=\"\" class=\"wp-image-385\" srcset=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/data-analysis-1.jpg 350w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/data-analysis-1-300x183.jpg 300w\" sizes=\"auto, (max-width: 350px) 100vw, 350px\" \/><figcaption class=\"vf-figure__caption\"><em>Data analysis approaches<\/em><\/figcaption><\/figure>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n\n\n\n<section class=\"vf-tabs__section\" id=\"vf-tabs__section-90de3259-335f-4a7f-b326-6decf64533f4\"><h2>Library design<\/h2>\n<div class=\"vf-grid | vf-grid__col-3\"><div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<ul class=\"wp-block-list\"><li>Diversity and similarity tools<\/li><li>Library creation<ul><li>For random screening<\/li><li>For specific targets<\/li><li>Exploration of SAR (iterative)<\/li><\/ul><\/li><\/ul>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<figure class=\"vf-figure wp-block-image size-large\"><a href=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"820\" height=\"601\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design.jpg\" alt=\"\" class=\"wp-image-395\" srcset=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design.jpg 820w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design-300x220.jpg 300w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design-768x563.jpg 768w\" sizes=\"auto, (max-width: 820px) 100vw, 820px\" \/><\/a><figcaption class=\"vf-figure__caption\">The probability to detect active compounds will be higher with a compound library designed to be diverse.\n\n<\/figcaption><\/figure>\n\n<\/div>\n<\/div>\n\n\n<div><!--[vf\/content]-->\n<div class=\"vf-content\">\n\n<figure class=\"vf-figure wp-block-image size-large\"><a href=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design02.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"820\" height=\"480\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design02.jpg\" alt=\"\" class=\"wp-image-396\" srcset=\"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design02.jpg 820w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design02-300x176.jpg 300w, https:\/\/www.embl.org\/groups\/chemical-biology\/wp-content\/uploads\/2020\/06\/library-design02-768x450.jpg 768w\" sizes=\"auto, (max-width: 820px) 100vw, 820px\" \/><\/a><figcaption class=\"vf-figure__caption\">Designing a focused compound library in order to learn about the structure-activity relationship and improve on molecular properties.\n\n<\/figcaption><\/figure>\n\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n\n\n\n<section class=\"vf-tabs__section\" id=\"vf-tabs__section-6fd98a15-07aa-4e0e-92ef-06809f90d615\"><h2>Compound acquisitions<\/h2>\n<ul class=\"wp-block-list\" id=\"block-9c1649f1-4559-4e3e-9400-d5128cb0c3eb\"><li>Identifying vendors and availability of desired compounds<\/li><li>Quote requests<\/li><\/ul>\n<\/section>\n<\/div><\/div>\n\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"template-title-left-aligned.php","meta":{"_acf_changed":false,"footnotes":""},"embl_taxonomy":[],"class_list":["post-351","page","type-page","status-publish","hentry"],"acf":[],"embl_taxonomy_terms":[],"_links":{"self":[{"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/pages\/351","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/comments?post=351"}],"version-history":[{"count":71,"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/pages\/351\/revisions"}],"predecessor-version":[{"id":1062,"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/pages\/351\/revisions\/1062"}],"wp:attachment":[{"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/media?parent=351"}],"wp:term":[{"taxonomy":"embl_taxonomy","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/chemical-biology\/wp-json\/wp\/v2\/embl_taxonomy?post=351"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}