Proteins: Structure, Function, and BioinformaticsVolume 78, Issue 9 p. 2029-2040 Research Article Sub-angstrom modeling of complexes between flexible peptides and globular proteins Barak Raveh, Barak Raveh Department of Microbiology and Molecular Genetics, Insitute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, Jerusalem, 91120 Israel The Blavatnik School of Computer Science, Tel-Aviv University, Ramat Aviv, 69978 Israel Barak Raveh and Nir London contributed equally to this work.Search for more papers by this authorNir London, Nir London Department of Microbiology and Molecular Genetics, Insitute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, Jerusalem, 91120 Israel Barak Raveh and Nir London contributed equally to this work.Search for more papers by this authorOra Schueler-Furman, Corresponding Author Ora Schueler-Furman [email protected] Department of Microbiology and Molecular Genetics, Insitute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, Jerusalem, 91120 IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, POB 12272, Jerusalem 91120 Israel===Search for more papers by this author Barak Raveh, Barak Raveh Department of Microbiology and Molecular Genetics, Insitute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, Jerusalem, 91120 Israel The Blavatnik School of Computer Science, Tel-Aviv University, Ramat Aviv, 69978 Israel Barak Raveh and Nir London contributed equally to this work.Search for more papers by this authorNir London, Nir London Department of Microbiology and Molecular Genetics, Insitute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, Jerusalem, 91120 Israel Barak Raveh and Nir London contributed equally to this work.Search for more papers by this authorOra Schueler-Furman, Corresponding Author Ora Schueler-Furman [email protected] Department of Microbiology and Molecular Genetics, Insitute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, Jerusalem, 91120 IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University, POB 12272, Jerusalem 91120 Israel===Search for more papers by this author First published: 18 March 2010 https://doi.org/10.1002/prot.22716Citations: 314 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract A wide range of regulatory processes in the cell are mediated by flexible peptides that fold upon binding to globular proteins. Computational efforts to model these interactions are hindered by the large number of rotatable bonds in flexible peptides relative to typical ligand molecules, and the fact that different peptides assume different backbone conformations within the same binding site. In this study, we present Rosetta FlexPepDock, a novel tool for refining coarse peptide–protein models that allows significant changes in both peptide backbone and side chains. We obtain high resolution models, often of sub-angstrom backbone quality, over an extensive and general benchmark that is based on a large nonredundant dataset of 89 peptide–protein interactions. Importantly, side chains of known binding motifs are modeled particularly well, typically with atomic accuracy. In addition, our protocol has improved modeling quality for the important application of cross docking to PDZ domains. We anticipate that the ability to create high resolution models for a wide range of peptide–protein complexes will have significant impact on structure-based functional characterization, controlled manipulation of peptide interactions, and on peptide-based drug design. Proteins 2010. © 2010 Wiley-Liss, Inc. Supporting Information Additional Supporting Information may be found in the online version of this article. Filename Description PROT_22716_sm_SuppFigures.pdf330.6 KB Supporting Information Figures. PROT_22716_sm_SuppTable1.pdf154.6 KB Supporting Information Table 1. PROT_22716_sm_SuppTable2.pdf244.3 KB Supporting Information Table 2. PROT_22716_sm_SuppTable3.pdf393.4 KB Supporting Information Table 3. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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Sub-angstrom modeling of complexes between flexible peptides and globular proteins

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