Scientific benchmarks for guiding macromolecular energy function improvement.


Journal Article

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).

Full Text

Duke Authors

Cited Authors

  • Leaver-Fay, A; O'Meara, MJ; Tyka, M; Jacak, R; Song, Y; Kellogg, EH; Thompson, J; Davis, IW; Pache, RA; Lyskov, S; Gray, JJ; Kortemme, T; Richardson, JS; Havranek, JJ; Snoeyink, J; Baker, D; Kuhlman, B

Published Date

  • 2013

Published In

Volume / Issue

  • 523 /

Start / End Page

  • 109 - 143

PubMed ID

  • 23422428

Pubmed Central ID

  • 23422428

Electronic International Standard Serial Number (EISSN)

  • 1557-7988

Digital Object Identifier (DOI)

  • 10.1016/B978-0-12-394292-0.00006-0


  • eng

Conference Location

  • United States