H-bond network optimization in protein-protein complexes: Are all-atom force field scores enough?

Diego Masone, Israel Cabeza de Vaca, Carles Pons, Juan Fernandez Recio, Victor Guallar

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Structural prediction of protein-protein complexes given the structures of the two interacting compounds in their unbound state is a key problem in biophysics. In addition to the problem of sampling of near-native orientations, one of the modeling main difficulties is to discriminate true from false positives. Here, we present a hierarchical protocol for docking refinement able to discriminate near native poses from a group of docking candidates. The main idea is to combine an efficient sampling of the full system hydrogen bond network and side chains, together with an all-atom force field and a surface generalized born implicit solvent. We tested our method on a set of twenty two complexes containing a near-native solution within the top 100 docking poses, obtaining a near native solution as the top pose in 70% of the cases. We show that all atom force fields optimized H-bond networks do improve significantly state of the art scoring functions.

Original languageEnglish (US)
Pages (from-to)818-824
Number of pages7
JournalProteins: Structure, Function and Bioinformatics
Volume80
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • Docking refinement
  • Hierarchical protocol
  • Implicit solvent
  • Near-native solutions

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