RosettaDock in CAPRI rounds 6-12

TitleRosettaDock in CAPRI rounds 6-12
Publication TypeJournal Article
Year of Publication2007
AuthorsWang, C., Schueler-Furman O., Andre I., London N., Fleishman S. J., Bradley P., Qian B., & Baker D.
JournalProteins
Volume69
Issue4
Pagination758-63
Date Published2007 Dec 1
ISSN1097-0134
KeywordsAlgorithms, Catalytic Domain, Computational Biology, Computer Simulation, Databases, Protein, Dimerization, Escherichia coli, Molecular Conformation, Monte Carlo Method, Primary Publication, Protein Binding, Protein Conformation, Protein Interaction Mapping, Proteins, Proteomics, Software
Abstract

A challenge in protein-protein docking is to account for the conformational changes in the monomers that occur upon binding. The RosettaDock method, which incorporates sidechain flexibility but keeps the backbone fixed, was found in previous CAPRI rounds (4 and 5) to generate docking models with atomic accuracy, provided that conformational changes were mainly restricted to protein sidechains. In the recent rounds of CAPRI (6-12), large backbone conformational changes occur upon binding for several target complexes. To address these challenges, we explicitly introduced backbone flexibility in our modeling procedures by combining rigid-body docking with protein structure prediction techniques such as modeling variable loops and building homology models. Encouragingly, using this approach we were able to correctly predict a significant backbone conformational change of an interface loop for Target 20 (12 A rmsd between those in the unbound monomer and complex structures), but accounting for backbone flexibility in protein-protein docking is still very challenging because of the significantly larger conformational space, which must be surveyed. Motivated by these CAPRI challenges, we have made progress in reformulating RosettaDock using a "fold-tree" representation, which provides a general framework for treating a wide variety of flexible-backbone docking problems.

Alternate JournalProteins
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