Scientific benchmarks for guiding macromolecular energy function improvement.

TitleScientific benchmarks for guiding macromolecular energy function improvement.
Publication TypeJournal Article
Year of Publication2013
AuthorsLeaver-Fay, A., O'Meara M. J., Tyka M., Jacak R., Song Y., Kellogg E. H., Thompson J., Davis I. W., Pache R. A., Lyskov S., Gray J. J., Kortemme T., Richardson J. S., Havranek J. J., Snoeyink J., Baker D., & Kuhlman B.
JournalMethods in enzymology
Volume523
Pagination109-43
Date Published2013
ISSN1557-7988
KeywordsCollaborative Publication
Abstract

Accurate energy functions are critical to macromolecular modeling and design. We describe new tools for identifying inaccuracies in energy functions and guiding their improvement, and illustrate the application of these tools to the improvement of the Rosetta energy function. The feature analysis tool identifies discrepancies between structures deposited in the PDB and low-energy structures generated by Rosetta; these likely arise from inaccuracies in the energy function. The optE tool optimizes the weights on the different components of the energy function by maximizing the recapitulation of a wide range of experimental observations. We use the tools to examine three proposed modifications to the Rosetta energy function: improving the unfolded state energy model (reference energies), using bicubic spline interpolation to generate knowledge-based torisonal potentials, and incorporating the recently developed Dunbrack 2010 rotamer library (Shapovalov & Dunbrack, 2011).

DOI10.1016/B978-0-12-394292-0.00006-0
Custom1

http://www.ncbi.nlm.nih.gov/pubmed/23422428?dopt=Abstract

Alternate JournalMeth. Enzymol.