TY - JOUR

T1 - A new scoring function for protein-protein docking that identifies native structures with unprecedented accuracy

AU - Moreira, Irina S.

AU - da Silva Martins, João Miguel

AU - Coimbra, João T.S.

AU - Ramos, Maria J.

AU - Fernandes, Pedro A.

PY - 2015

Y1 - 2015

N2 - 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. This journal is

AB - 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. This journal is

U2 - 10.1039/c4cp04688a

DO - 10.1039/c4cp04688a

M3 - Journal article

C2 - 25490550

AN - SCOPUS:84919807951

VL - 17

SP - 2378

EP - 2387

JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

SN - 1463-9076

IS - 4

ER -