title: A new scoring function for protein-protein docking that identifies native structures with unprecedented accuracy.
abstract: Protein-protein (P-P) 3D structures are fundamental to structural biology and drug discovery. However, most of them have never been determined. Many docking algorithms were developed for that purpose, but they have a very limited accuracy in generating native-like structures and identifying the most correct one, in particular when a single answer is asked for. With such a low success rate it is difficult to point out one docked structure as being native-like. Here we present a new, high accuracy, scoring method to identify the 3D structure of P-P complexes among a set of trial poses. It incorporates alanine scanning mutagenesis experimental data that need to be obtained a priori. The scoring scheme works by matching the computational and the experimental alanine scanning mutagenesis results. The size of the trial P-P interface area is also taken into account. We show that the method ranks the trial structures and identifies the native-like structures with unprecedented accuracy (∼94%), providing the correct P-P 3D structures that biochemists and molecular biologists need to pursue their studies. With such a success rate, the bottleneck of protein-protein docking moves from the scoring to searching algorithms.
authors.affiliation: REQUIMTE/Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal. pafernan@fc.up.pt.
authors.forename: Irina S
authors.initials: IS
authors.lastname: Moreira
authors.forename: João M
authors.initials: JM
authors.lastname: Martins
authors.forename: João T S
authors.initials: JT
authors.lastname: Coimbra
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramos
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Fernandes
mesh_terms: D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012984:Software
chemical_list: D011506:Proteins