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Download fileCombined Covalent-Electrostatic Model of Hydrogen Bonding Improves Structure Prediction with Rosetta
journal contribution
posted on 2015-02-10, 00:00 authored by Matthew J. O’Meara, Andrew Leaver-Fay, Michael D. Tyka, Amelie Stein, Kevin Houlihan, Frank DiMaio, Philip Bradley, Tanja Kortemme, David Baker, Jack Snoeyink, Brian KuhlmanInteractions
between polar atoms are challenging to model because at very short
ranges they form hydrogen bonds (H-bonds) that are partially covalent
in character and exhibit strong orientation preferences; at longer
ranges the orientation preferences are lost, but significant electrostatic
interactions between charged and partially charged atoms remain. To
simultaneously model these two types of behavior, we refined an orientation
dependent model of hydrogen bonds [Kortemme et al. J. Mol. Biol. 2003, 326, 1239] used by the molecular
modeling program Rosetta and then combined it with a distance-dependent
Coulomb model of electrostatics. The functional form of the H-bond
potential is physically motivated and parameters are fit so that H-bond
geometries that Rosetta generates closely resemble H-bond geometries
in high-resolution crystal structures. The combined potentials improve
performance in a variety of scientific benchmarks including decoy
discrimination, side chain prediction, and native sequence recovery
in protein design simulations and establishes a new standard energy
function for Rosetta.