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

PROTEINS: STRUCTURE, FUNCTION AND GENETICS

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2012 vol. 80 p. 818 - 824

0887-3585

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.