{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:55:57Z","timestamp":1778651757007,"version":"3.51.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T00:00:00Z","timestamp":1502668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M019829\/1"],"award-info":[{"award-number":["BB\/M019829\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>A deleterious amino acid change in a protein can be compensated by a second-site rescue mutation. These compensatory mechanisms can be mimicked by drugs. In particular, the location of rescue mutations can be used to identify protein regions that can be targeted by small molecules to reactivate a damaged mutant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We present the first general computational method to detect rescue sites. By mimicking the effect of mutations through the application of forces, the double force scanning (DFS) method identifies the second-site residues that make the protein structure most resilient to the effect of pathogenic mutations. We tested DFS predictions against two datasets containing experimentally validated and putative evolutionary-related rescue sites. A remarkably good agreement was found between predictions and experimental data. Indeed, almost half of the rescue sites in p53 was correctly predicted by DFS, with 65% of remaining sites in contact with DFS predictions. Similar results were found for other proteins in the evolutionary dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The DFS code is available under GPL at https:\/\/fornililab.github.io\/dfs\/<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx515","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T15:14:46Z","timestamp":1502378086000},"page":"207-214","source":"Crossref","is-referenced-by-count":11,"title":["<i>In silico<\/i>\n                    identification of rescue sites by double force scanning"],"prefix":"10.1093","volume":"34","author":[{"given":"Matteo","family":"Tiberti","sequence":"first","affiliation":[{"name":"School of Biological and Chemical Sciences, Queen Mary University of London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Pandini","sequence":"additional","affiliation":[{"name":"Department of Computer Science, College of Engineering, Design and Physical Sciences and Synthetic Biology Theme, Institute of Environment, Health and Societies, Brunel University London, Uxbridge, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franca","family":"Fraternali","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biophysics, King\u2018s College London, London, UK"},{"name":"The Francis Crick Institute, London, UK"},{"name":"The Thomas Young Centre for Theory and Simulation of Materials, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Fornili","sequence":"additional","affiliation":[{"name":"School of Biological and Chemical Sciences, Queen Mary University of London, London, UK"},{"name":"The Thomas Young Centre for Theory and Simulation of Materials, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,8,14]]},"reference":[{"key":"2023012712233882300_btx515-B1","doi-asserted-by":"crossref","first-page":"e1000544","DOI":"10.1371\/journal.pcbi.1000544","article-title":"Perturbation-response scanning reveals ligand entry-exit mechanisms of ferric binding protein","volume":"5","author":"Atilgan","year":"2009","journal-title":"PLoS Comput. 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