{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T21:58:24Z","timestamp":1771019904741,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1490,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Protein movements form a continuum from large domain rearrangements (including folding and restructuring) to side-chain rotamer changes and small rearrangements. Understanding side-chain flexibility upon binding is important to understand molecular recognition events and predict ligand binding.<\/jats:p>\n               <jats:p>Methods: In the present work, we developed a well-curated non-redundant dataset of 188 proteins in pairs of structures in the Apo (unbound) and Holo (bound) forms to study the extent and the factors that guide side-chain rotamer changes upon binding.<\/jats:p>\n               <jats:p>Results: Our analysis shows that side-chain rotamer changes are widespread with only 10% of binding sites displaying no conformational changes. Overall, at most five rotamer changes account for the observed movements in 90% of the cases. Furthermore, rotamer changes are essential in 32% of flexible binding sites. The different amino acids have a 11-fold difference in their probability to undergo changes. Side-chain flexibility represents an intrinsic property of amino acids as it correlates well with configurational entropy differences. Furthermore, on average b-factors and solvent accessible surface areas can discriminate flexible side-chains in the Apo form. Finally, there is a rearrangement of the hydrogen-bonding network upon binding primarily with a loss of H-bonds with water molecules and a gain of H-bonds with protein residues for flexible residues. Interestingly, only 25% of side chains capable of forming H-bonds do so with the ligand upon binding. In terms of drug design, this last result shows that there is a large number of potential interactions that may be exploited to modulate the specificity and sensitivity of inhibitors.<\/jats:p>\n               <jats:p>Contact: \u00a0rafael.najmanovich@usherbrooke.ca<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts395","type":"journal-article","created":{"date-parts":[[2012,9,7]],"date-time":"2012-09-07T20:35:22Z","timestamp":1347050122000},"page":"i423-i430","source":"Crossref","is-referenced-by-count":76,"title":["Side-chain rotamer changes upon ligand binding: common, crucial, correlate with entropy and rearrange hydrogen bonding"],"prefix":"10.1093","volume":"28","author":[{"given":"Francis","family":"Gaudreault","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universit\u00e9 de Sherbrooke, 3001, 12e Avenue Nord. Sherbrooke, Qu\u00e9bec, Canada J1H 5N4"}]},{"given":"Matthieu","family":"Chartier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universit\u00e9 de Sherbrooke, 3001, 12e Avenue Nord. Sherbrooke, Qu\u00e9bec, Canada J1H 5N4"}]},{"given":"Rafael","family":"Najmanovich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universit\u00e9 de Sherbrooke, 3001, 12e Avenue Nord. Sherbrooke, Qu\u00e9bec, Canada J1H 5N4"}]}],"member":"286","published-online":{"date-parts":[[2012,9,3]]},"reference":[{"key":"2023012513011303800_B1","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1021\/ja066980q","article-title":"Classification of water molecules in protein binding sites","volume":"129","author":"Barillari","year":"2007","journal-title":"J. Am. Chem. 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