Kresten Lindorff-Larsen and Stefano Piana contributed equally to this work.
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Research Article
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Improved side-chain torsion potentials for the Amber ff99SB protein force field
Article first published online: 9 MAR 2010
DOI: 10.1002/prot.22711
Copyright © 2010 Wiley-Liss, Inc.
Issue
1097-0134/asset/cover.gif?v=1&s=d817e79b67ba6cacf8bdcce1a819c04de300a7e3 "Proteins: Structure, Function, and Bioinformatics")
Proteins: Structure, Function, and Bioinformatics
Volume 78, Issue 8, pages 1950–1958, June 2010
Additional Information
How to Cite
Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J. L., Dror, R. O. and Shaw, D. E. (2010), Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins, 78: 1950–1958. doi: 10.1002/prot.22711
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Kresten Lindorff-Larsen and Stefano Piana contributed equally to this work.
Publication History
- Issue published online: 15 APR 2010
- Article first published online: 9 MAR 2010
- Accepted manuscript online: 9 MAR 2010 12:00AM EST
- Manuscript Accepted: 9 FEB 2010
- Manuscript Revised: 5 FEB 2010
- Manuscript Received: 11 DEC 2009
Keywords:
- molecular dynamics simulation;
- molecular mechanics;
- NMR;
- rotamer;
- side chain;
- protein dynamics;
- quantum mechanics;
- dihedral
Abstract
Recent advances in hardware and software have enabled increasingly long molecular dynamics (MD) simulations of biomolecules, exposing certain limitations in the accuracy of the force fields used for such simulations and spurring efforts to refine these force fields. Recent modifications to the Amber and CHARMM protein force fields, for example, have improved the backbone torsion potentials, remedying deficiencies in earlier versions. Here, we further advance simulation accuracy by improving the amino acid side-chain torsion potentials of the Amber ff99SB force field. First, we used simulations of model alpha-helical systems to identify the four residue types whose rotamer distribution differed the most from expectations based on Protein Data Bank statistics. Second, we optimized the side-chain torsion potentials of these residues to match new, high-level quantum-mechanical calculations. Finally, we used microsecond-timescale MD simulations in explicit solvent to validate the resulting force field against a large set of experimental NMR measurements that directly probe side-chain conformations. The new force field, which we have termed Amber ff99SB-ILDN, exhibits considerably better agreement with the NMR data. Proteins 2010. © 2010 Wiley-Liss, Inc.