Rosetta in CAPRI rounds 13-19.

Publication Type:

Journal Article

Source:

Proteins, Volume 78, Issue 15, p.3212-8 (2010)

Keywords:

2010, Center-Authored Paper, Computational Biology, Models, Chemical, Models, Molecular, Monte Carlo Method, Protein Binding, Protein Interaction Mapping, Public Health Sciences Division, RNA, RNA-Binding Proteins, Software

Abstract:

Modeling the conformational changes that occur on binding of macromolecules is an unsolved challenge. In previous rounds of the Critical Assessment of PRediction of Interactions (CAPRI), it was demonstrated that the Rosetta approach to macromolecular modeling could capture side chain conformational changes on binding with high accuracy. In rounds 13-19 we tested the ability of various backbone remodeling strategies to capture the main-chain conformational changes observed during binding events. These approaches span a wide range of backbone motions, from limited refinement of loops to relieve clashes in homologous docking, through extensive remodeling of loop segments, to large-scale remodeling of RNA. Although the results are encouraging, major improvements in sampling and energy evaluation are clearly required for consistent high accuracy modeling. Analysis of our failures in the CAPRI challenges suggest that conformational sampling at the termini of exposed beta strands is a particularly pressing area for improvement.