Combined covalent-electrostatic model of hydrogen bonding improves structure prediction with Rosetta

TY - JOUR

T1 - Combined covalent-electrostatic model of hydrogen bonding improves structure prediction with Rosetta

AU - O'Meara, Matthew J

AU - Leaver-Fay, Andrew

AU - Tyka, Michael D

AU - Stein, Amelie

AU - Houlihan, Kevin

AU - DiMaio, Frank

AU - Bradley, Philip

AU - Kortemme, Tanja

AU - Baker, David

AU - Snoeyink, Jack

AU - Kuhlman, Brian

PY - 2015/2/10

Y1 - 2015/2/10

N2 - Interactions 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.

AB - Interactions 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.

KW - Hydrogen Bonding

KW - Models, Chemical

KW - Models, Molecular

KW - Molecular Structure

KW - Software

KW - Static Electricity

U2 - 10.1021/ct500864r

DO - 10.1021/ct500864r

M3 - Journal article

C2 - 25866491

SN - 1549-9618

VL - 11

SP - 609

EP - 622

JO - Journal of Chemical Theory and Computation

JF - Journal of Chemical Theory and Computation

IS - 2

ER -