Dmitri Beglov and David Hall contributed equally to this article.
Minimal ensembles of side chain conformers for modeling protein–protein interactions
Article first published online: 22 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 80, Issue 2, pages 591–601, February 2012
How to Cite
Beglov, D., Hall, D. R., Brenke, R., Shapovalov, M. V., Dunbrack, R. L., Kozakov, D. and Vajda, S. (2012), Minimal ensembles of side chain conformers for modeling protein–protein interactions. Proteins, 80: 591–601. doi: 10.1002/prot.23222
- Issue published online: 10 JAN 2012
- Article first published online: 22 NOV 2011
- Accepted manuscript online: 18 OCT 2011 04:13AM EST
- Manuscript Accepted: 22 SEP 2011
- Manuscript Revised: 12 SEP 2011
- Manuscript Received: 31 MAY 2011
- National Institute of General Medical Sciences. Grant Numbers: GM061867, GM093147, GM064700, GM84453
- rotamer libraries;
- side chain flexibility;
- protein binding;
- structure prediction;
- pre existing ensemble of conformers
The goal of this article is to reduce the complexity of the side chain search within docking problems. We apply six methods of generating side chain conformers to unbound protein structures and determine their ability of obtaining the bound conformation in small ensembles of conformers. Methods are evaluated in terms of the positions of side chain end groups. Results for 68 protein complexes yield two important observations. First, the end-group positions change less than 1 Å on association for over 60% of interface side chains. Thus, the unbound protein structure carries substantial information about the side chains in the bound state, and the inclusion of the unbound conformation into the ensemble of conformers is very beneficial. Second, considering each surface side chain separately in its protein environment, small ensembles of low-energy states include the bound conformation for a large fraction of side chains. In particular, the ensemble consisting of the unbound conformation and the two highest probability predicted conformers includes the bound conformer with an accuracy of 1 Å for 78% of interface side chains. As more than 60% of the interface side chains have only one conformer and many others only a few, these ensembles of low-energy states substantially reduce the complexity of side chain search in docking problems. This approach was already used for finding pockets in protein–protein interfaces that can bind small molecules to potentially disrupt protein–protein interactions. Side-chain search with the reduced search space will also be incorporated into protein docking algorithms. Proteins 2012. © 2011 Wiley Periodicals, Inc.