{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T20:50:49Z","timestamp":1773175849052,"version":"3.50.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-GM078221"],"award-info":[{"award-number":["R01-GM078221"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1507736"],"award-info":[{"award-number":["1507736"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Binding-induced conformational changes challenge current computational docking algorithms by exponentially increasing the conformational space to be explored. To restrict this search to relevant space, some computational docking algorithms exploit the inherent flexibility of the protein monomers to simulate conformational selection from pre-generated ensembles. As the ensemble size expands with increased flexibility, these methods struggle with efficiency and high false positive rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we develop and benchmark RosettaDock 4.0, which efficiently samples large conformational ensembles of flexible proteins and docks them using a novel, six-dimensional, coarse-grained score function. A strong discriminative ability allows an eight-fold higher enrichment of near-native candidate structures in the coarse-grained phase compared to RosettaDock 3.2. It adaptively samples 100 conformations each of the ligand and the receptor backbone while increasing computational time by only 20\u201380%. In local docking of a benchmark set of 88 proteins of varying degrees of flexibility, the expected success rate (defined as cases with\u2009\u226550% chance of achieving 3 near-native structures in the 5 top-ranked ones) for blind predictions after resampling is 77% for rigid complexes, 49% for moderately flexible complexes and 31% for highly flexible complexes. These success rates on flexible complexes are a substantial step forward from all existing methods. Additionally, for highly flexible proteins, we demonstrate that when a suitable conformer generation method exists, the method successfully docks the complex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>As a part of the Rosetta software suite, RosettaDock 4.0 is available at https:\/\/www.rosettacommons.org to all non-commercial users for free and to commercial users for a fee.<\/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\/bty355","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T15:10:38Z","timestamp":1524841838000},"page":"3461-3469","source":"Crossref","is-referenced-by-count":175,"title":["Efficient flexible backbone protein\u2013protein docking for challenging targets"],"prefix":"10.1093","volume":"34","author":[{"given":"Nicholas A","family":"Marze","sequence":"first","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-9104","authenticated-orcid":false,"given":"Shourya S","family":"Roy Burman","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA"}]},{"given":"William","family":"Sheffler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Washington, Seattle, WA, USA"},{"name":"Institute for Protein Design, University of Washington, Seattle, WA, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-2324","authenticated-orcid":false,"given":"Jeffrey J","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA"},{"name":"Program in Molecular Biophysics, Johns Hopkins University, Baltimore, MD, USA"},{"name":"Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA"},{"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA"}]}],"member":"286","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"2023012712432423000_bty355-B1","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1021\/acs.jctc.7b00125","article-title":"The Rosetta all-atom energy function for macromolecular modeling and design","volume":"13","author":"Alford","year":"2017","journal-title":"J. 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