{"id":6703,"date":"2015-01-14T10:51:52","date_gmt":"2015-01-14T09:51:52","guid":{"rendered":"http:\/\/www.h-its.org\/?p=6703"},"modified":"2019-06-06T11:42:46","modified_gmt":"2019-06-06T09:42:46","slug":"structure-based-drug-discovery","status":"publish","type":"hits-project","link":"https:\/\/www.h-its.org\/de\/projects\/structure-based-drug-discovery\/","title":{"rendered":"Structure-based drug discovery"},"content":{"rendered":"\n<p>Proteins are dynamic and constantly changing their shape. This flexibility not only presents a challenge to to structure-based drug design approaches but also opportunities for the design of specific compounds with suitable kinetic properties. We are developing methods to model and simulate protein and ligand dynamics in order to identify transient binding pockets in proteins and to compute the kinetics of drug binding.<\/p>\n\n\n\n<p><a title=\"TRAPP is a Tool for Analysis of Transient Binding Pockets in Proteins\" href=\"http:\/\/mcm.h-its.org\/trapp\" target=\"_blank\" rel=\"noopener noreferrer\">TRAPP is a Tool for Analysis of Transient Binding Pockets in Proteins<\/a>. It automates the tracking, analysis, and visualization of binding pocket variations along a protein motion trajectory or within an ensemble of protein structures.&nbsp; TRAPP thus enables an assessment of the druggability of a disease-related target protein taking its flexibility into account. See <a title=\"Kokh et al, JCIM 2013\" href=\"http:\/\/pubs.acs.org\/doi\/abs\/10.1021\/ci4000294\" target=\"_blank\" rel=\"noopener noreferrer\">Kokh et al, J. Chem. Inf. Model., 2013<\/a>. To efficiently generate protein conformations that reveal transient pockets, we are developing two methods based on the Rotationally-induced perturbation (RIP) simulation method: L-RIP and RIPlig (Kokh et al., in prep).<\/p>\n\n\n\n<p>The importance of binding kinetics for drug discovery has recently become appreciated. In the <a title=\"K4DD\" href=\"http:\/\/www.k4dd.eu\" target=\"_blank\" rel=\"noopener noreferrer\">K4DD<\/a> IMI project, we are developing methods to simulated protein-drug binding and unbinding processes and to predict the corresponding on-rates and off-rates.<\/p>\n\n\n\n<p>We apply computational methods to challenging drug discovery problems. For example, in the <a title=\"nmtrypi\" href=\"http:\/\/www.nmtrypi.eu\" target=\"_blank\" rel=\"noopener noreferrer\">NMTRypI New Medicines for Trypanosomal Infections<\/a> EU project, the goal is to develop new candidate drugs against neglected parasitic diseases such as leishmaniasis.<\/p>\n","protected":false},"author":6,"featured_media":29726,"template":"","hits-research-group":[1298],"hits-project-category":[],"class_list":["post-6703","hits-project","type-hits-project","status-publish","has-post-thumbnail","hentry","hits-research-group-mcm-de"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Structure-based drug discovery - HITS gGmbH<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.h-its.org\/de\/projects\/structure-based-drug-discovery\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Structure-based drug discovery - HITS gGmbH\" \/>\n<meta property=\"og:description\" content=\"Proteins are dynamic and constantly changing their shape. This flexibility not only presents a challenge to to structure-based drug design approaches ...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.h-its.org\/de\/projects\/structure-based-drug-discovery\/\" \/>\n<meta property=\"og:site_name\" content=\"HITS gGmbH\" \/>\n<meta property=\"article:modified_time\" content=\"2019-06-06T09:42:46+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.h-its.org\/de\/wp-content\/uploads\/sites\/2\/2015\/01\/10.1021_ci4000294_ref_2.png\" \/>\n\t<meta property=\"og:image:width\" content=\"1600\" \/>\n\t<meta property=\"og:image:height\" content=\"1252\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Gesch\u00e4tzte Lesezeit\" \/>\n\t<meta name=\"twitter:data1\" content=\"1\u00a0Minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/structure-based-drug-discovery\\\/\",\"url\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/structure-based-drug-discovery\\\/\",\"name\":\"Structure-based drug discovery - HITS gGmbH\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/structure-based-drug-discovery\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/structure-based-drug-discovery\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/wp-content\\\/uploads\\\/sites\\\/2\\\/2015\\\/01\\\/10.1021_ci4000294_ref_2.png\",\"datePublished\":\"2015-01-14T09:51:52+00:00\",\"dateModified\":\"2019-06-06T09:42:46+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/structure-based-drug-discovery\\\/#breadcrumb\"},\"inLanguage\":\"de\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/structure-based-drug-discovery\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"de\",\"@id\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/structure-based-drug-discovery\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/wp-content\\\/uploads\\\/sites\\\/2\\\/2015\\\/01\\\/10.1021_ci4000294_ref_2.png\",\"contentUrl\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/wp-content\\\/uploads\\\/sites\\\/2\\\/2015\\\/01\\\/10.1021_ci4000294_ref_2.png\",\"width\":1600,\"height\":1252,\"caption\":\"TRAPP helps to find transient pockets in proteins\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/structure-based-drug-discovery\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Projects\",\"item\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/projects\\\/\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Structure-based drug discovery\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/#website\",\"url\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/\",\"name\":\"HITS gGmbH\",\"description\":\"Heidelberg Institute for Theoretical Studies\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.h-its.org\\\/de\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"de\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Structure-based drug discovery - HITS gGmbH","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.h-its.org\/de\/projects\/structure-based-drug-discovery\/","og_locale":"de_DE","og_type":"article","og_title":"Structure-based drug discovery - HITS gGmbH","og_description":"Proteins are dynamic and constantly changing their shape. 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