title: H-bond network optimization in protein-protein complexes: are all-atom force field scores enough?
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.
authors: Joint BSC-IRB Research Program in Computational Biology. Barcelona, Spain Supercomputing Center, 08034 Barcelona, Spain.
authors: Diego
authors: D
authors: Masone
authors: Israel Cabeza de
authors: IC
authors: Vaca
authors: Carles
authors: C
authors: Pons
authors: Juan Fernandez
authors: JF
authors: Recio
authors: Victor
authors: V
authors: Guallar
mesh_terms: D003198:Computer Simulation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry
chemical_list: D011506:Proteins; D012997:Solvents