title: Scientific benchmarks for guiding macromolecular energy function improvement.
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).
authors: Department of Biochemistry, University of North Carolina, Chapel Hill, North Carolina, USA. leaverfa@email.unc.edu
authors: Andrew
authors: A
authors: Leaver-Fay
authors: Matthew J
authors: MJ
authors: O'Meara
authors: Mike
authors: M
authors: Tyka
authors: Ron
authors: R
authors: Jacak
authors: Yifan
authors: Y
authors: Song
authors: Elizabeth H
authors: EH
authors: Kellogg
authors: James
authors: J
authors: Thompson
authors: Ian W
authors: IW
authors: Davis
authors: Roland A
authors: RA
authors: Pache
authors: Sergey
authors: S
authors: Lyskov
authors: Jeffrey J
authors: JJ
authors: Gray
authors: Tanja
authors: T
authors: Kortemme
authors: Jane S
authors: JS
authors: Richardson
authors: James J
authors: JJ
authors: Havranek
authors: Jack
authors: J
authors: Snoeyink
authors: David
authors: D
authors: Baker
authors: Brian
authors: B
authors: Kuhlman
mesh_terms: D000465:Algorithms; D046911:Macromolecular Substances / Q000737:chemistry*; D011487:Protein Conformation; D012984:Software
chemical_list: D046911:Macromolecular Substances