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. Proteins 2010. © Wiley-Liss, Inc.
Highlights
The conformations of biological macromolecules often change on complex formation with binding partners
The energetic differences associated with changes in backbone configurations can be subtle, and the space of even local conformational perturbations when combined with alternative docking arrangements is vast, making the accurate modeling of conformational changes on binding extremely challenging
T30: Rnd1–guanosine triphosphate (GTP) binding to plexin B1 modeling to small-molecule docking to RNA de novo modeling
Summary
The conformations of biological macromolecules often change on complex formation with binding partners. The most conservative strategy involved eliminating an extended loop that plexin uses for homodimerization [encompassing residues 1822–1834 according to the numbering in Protein Data Bank (PDB) entry 2REX4] followed by fixedbackbone docking to identify low-energy conformations.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
