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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

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

Revista

Título: Physical Chemistry Chemical Physics

Vol. 17

Páginas: 2378-2387

ISSN: 1463-9076

Editora: Royal Society of Chemistry

Indexação

ISI Web of Knowledge - 10 Citações

Scopus - 14 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10