{"id":3008,"date":"2016-06-15T12:29:59","date_gmt":"2016-06-15T11:29:59","guid":{"rendered":"http:\/\/www.blopig.com\/blog\/?p=3008"},"modified":"2016-06-15T12:29:59","modified_gmt":"2016-06-15T11:29:59","slug":"identifying-allosteric-hotspots-with-dynamics-using-molecular-simulation-to-find-critical-sites-for-the-functional-motions-in-proteins","status":"publish","type":"post","link":"https:\/\/www.blopig.com\/blog\/2016\/06\/identifying-allosteric-hotspots-with-dynamics-using-molecular-simulation-to-find-critical-sites-for-the-functional-motions-in-proteins\/","title":{"rendered":"“Identifying Allosteric Hotspots with Dynamics”: Using molecular simulation to find critical sites for the functional motions in proteins"},"content":{"rendered":"

Allosteric (allo-(“other”) + steric (repulsion of atoms due to closeness or arrangement)) sites regulate protein function from a position other than the active site or binding site. Consider the latch on a pair of gardening scissors (Figure 1): depending on the\u00a0position of the latch (allosteric site)\u00a0the blades are prevented from cutting things at the other end (active site).<\/p>\n

\"secateurs-garden-shears-012\"<\/a>

Figure 1 Allostery explained: A safety latch\u00a0in gardening scissors.<\/p><\/div>\n

Due to the non-trivial positions of allosteric sites in proteins their\u00a0identification has been challenging. Selected well characterised\u00a0systems\u00a0such as GPCRs have known allosteric sites that are being used as targets in drug development. However, large scale identification of allosteric sites across the Protein Data Base (PDB) has not yet been feasible, partly because of the lack of tools.<\/p>\n

To tackle this problem the Gerstein Lab developed a computational protocol based on various molecular simulations and network methods to find allosteric hotspots in proteins across the PDB. They introduce two different pipelines; one for identifying allosteric residues on the surface (surface-critical) and one for buried residues (interior-critical).<\/p>\n

For the search of exterior-critical residues they us MC simulations to repeatedly probe the surface of the protein with short Monte Carlo (MC) with a short\u00a0peptide. Based on hard spheres and simple energy calculations this method seems to be\u00a0an efficient way\u00a0of detecting possible binding pockets.\u00a0Once the binding pockets have been found, the collective motions of the structure are\u00a0simulated using an elastic mass-and-spring network (an anisotropic network model [ANM]). Binding pockets that undergo significant deformation during these simulations are considered to be surface-critical.<\/p>\n

For interior-critical residues they\u00a0start by\u00a0weighting residue-residue contacts on the basis of collective\u00a0movement. Communities within the weighted network are then identified and the residues with the highest\u00a0betweenness interactions between communities are chosen\u00a0as interior-critical residues. Thus, interior-critical residues have\u00a0the highest information flow between two densely inter-connected groups of residues.<\/p>\n

The protocol as been implemented in\u00a0STRESS (STRucturally identified ESSential residues) and\u00a0is freely available at\u00a0stress.molmovdb.org.<\/p>\n

Publication:\u00a0http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27066750<\/p>\n","protected":false},"excerpt":{"rendered":"

Allosteric (allo-(“other”) + steric (repulsion of atoms due to closeness or arrangement)) sites regulate protein function from a position other than the active site or binding site. Consider the latch on a pair of gardening scissors (Figure 1): depending on the\u00a0position of the latch (allosteric site)\u00a0the blades are prevented from cutting things at the other […]<\/p>\n","protected":false},"author":29,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"nf_dc_page":"","wikipediapreview_detectlinks":true,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"ngg_post_thumbnail":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"ppma_author":[519],"class_list":["post-3008","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"authors":[{"term_id":519,"user_id":29,"is_guest":0,"slug":"samuel","display_name":"Samuel Demharter","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/9a7fc311ca91aec48d77ebd689fe2070f28c5442207cffd3adbd026c24de4d17?s=96&d=mm&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/3008","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/users\/29"}],"replies":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/comments?post=3008"}],"version-history":[{"count":1,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/3008\/revisions"}],"predecessor-version":[{"id":3010,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/3008\/revisions\/3010"}],"wp:attachment":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/media?parent=3008"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/categories?post=3008"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/tags?post=3008"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/ppma_author?post=3008"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}