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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Matthew J O'Meara
  • Andrew Leaver-Fay
  • Michael D Tyka
  • Stein, Amelie
  • Kevin Houlihan
  • Frank DiMaio
  • Philip Bradley
  • Tanja Kortemme
  • David Baker
  • Jack Snoeyink
  • Brian Kuhlman

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.

Original languageEnglish
JournalJournal of Chemical Theory and Computation
Volume11
Issue number2
Pages (from-to)609-622
Number of pages14
ISSN1549-9618
DOIs
Publication statusPublished - 2015
Externally publishedYes

    Research areas

  • Hydrogen Bonding, Models, Chemical, Models, Molecular, Molecular Structure, Software, Static Electricity

ID: 203256291