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

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Irina S Moreira (Author) Other; Joao M Martins (Author) Other; Joa T S Coimbra (Author) Other; Maria J Ramos (Author) FCUP; Pedro A Fernandes (Author) FCUP

Journal

Title: Physical Chemistry Chemical Physics

Vol. 17

Pages: 2378-2387

ISSN: 1463-9076

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 13 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-00A-3NP

DOI: 10.1039/c4cp04688a

Abstract (EN): 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 (similar to 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10