{"id":428,"date":"2014-03-13T11:32:46","date_gmt":"2014-03-13T03:32:46","guid":{"rendered":"http:\/\/www.huanglab.org.cn\/wordpress\/?p=428"},"modified":"2014-03-13T11:44:16","modified_gmt":"2014-03-13T03:44:16","slug":"incorporating-replacement-free-energy-of-binding-site-waters-in-molecular-docking","status":"publish","type":"post","link":"https:\/\/www.huanglab.org.cn\/wordpress\/?p=428","title":{"rendered":"Incorporating replacement free energy of binding-site waters in molecular docking"},"content":{"rendered":"<h1><\/h1>\n<h1><\/h1>\n<h1><a href=\"http:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2014\/03\/prot24530-fig-0002.png\"><img loading=\"lazy\" class=\"alignnone size-medium wp-image-429\" alt=\"prot24530-fig-0002\" src=\"http:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2014\/03\/prot24530-fig-0002-300x159.png\" width=\"300\" height=\"159\" srcset=\"https:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2014\/03\/prot24530-fig-0002-300x159.png 300w, https:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2014\/03\/prot24530-fig-0002.png 635w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/a><\/h1>\n<h1><\/h1>\n<p><a href=\"http:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2014\/03\/prot24530-fig-0006.png\"><img loading=\"lazy\" class=\"alignnone size-medium wp-image-440\" alt=\"prot24530-fig-0006\" src=\"http:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2014\/03\/prot24530-fig-0006-300x114.png\" width=\"300\" height=\"114\" srcset=\"https:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2014\/03\/prot24530-fig-0006-300x114.png 300w, https:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2014\/03\/prot24530-fig-0006.png 535w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/a><\/p>\n<p><a title=\"Incorporating replacement free energy of binding-site waters in molecular docking\" href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prot.24530\/full\" target=\"_blank\">Incorporating replacement free energy of binding-site waters in molecular docking<\/a><\/p>\n<p>Hanzi Sun<sup>1,2<\/sup>,Lifeng Zhao<sup>2<\/sup>,Shiming Peng<sup>2<\/sup>,Niu Huang<sup>1,2,*<\/sup><\/p>\n<p>1. College of Life Sciences, Beijing Normal University, Beijing, China<br \/>\n2. National Institute of Biological Sciences, Beijing, Zhongguancun Life Science Park, Beijing, China<\/p>\n<p>*Correspondence to: Niu Huang, National Institute of Biological Sciences, Beijing, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China. E-mail: huangniu#nibs.ac.cn<\/p>\n<p>ABSTRACT<\/p>\n<p>Binding-site water molecules play a crucial role in protein-ligand recognition, either being displaced upon ligand binding or forming water bridges to stabilize the complex. However, rigorously treating explicit binding-site waters is challenging in molecular docking, which requires to fully sample ensembles of waters and to consider the free energy cost of replacing waters. Here, we describe a method to incorporate structural and energetic properties of binding-site waters into molecular docking. We first developed a solvent property analysis (SPA) program to compute the replacement free energies of binding-site water molecules by post-processing molecular dynamics trajectories obtained from ligand-free protein structure simulation in explicit water. Next, we implemented a distance-dependent scoring term into DOCK scoring function to take account of the water replacement free energy cost upon ligand binding. We assessed this approach in protein targets containing important binding-site waters, and we demonstrated that our approach is reliable in reproducing the crystal binding geometries of protein-ligand-water complexes, as well as moderately improving the ligand docking enrichment performance. In addition, SPA program (free available to academic users upon request) may be applied in identifying hot-spot binding-site residues and structure-based lead optimization.Proteins 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Incorporating replacement free energy of binding-site waters in molecular docking Hanzi Sun1,2,Lifeng Zhao2,Shiming Peng2,Niu Huang1,2,* 1. College of Life Sciences, Beijing Normal University, Beijing, China 2. National Institute of Biological Sciences, Beijing, Zhongguancun Life Science Park, Beijing, China *Correspondence to: Niu Huang, National Institute of Biological Sciences, Beijing, No. 7 Science Park Road, Zhongguancun Life [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"ngg_post_thumbnail":0},"categories":[],"tags":[],"_links":{"self":[{"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/428"}],"collection":[{"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=428"}],"version-history":[{"count":12,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/428\/revisions"}],"predecessor-version":[{"id":432,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/428\/revisions\/432"}],"wp:attachment":[{"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=428"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=428"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=428"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}