Local Geometry and Evolutionary Conservation of Protein Surfaces Reveal the Multiple Recognition Patches in Protein-Protein Interactions

• DOI: 10.1371/journal.pcbi.1004580
• Publication Date: 2015-12-21T18:39:20Z
• Authors: Elodie Laine; Alessandra Carbone
• Keywords: Sequence (biology); Conserved sequence; Protein sequencing

Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins binding multiple partners. Contrary machine learning approaches, our combines in rational very straightforward way three sequence- structure-based descriptors of protein residues: evolutionary conservation, physico-chemical properties local geometry. The implemented strategy yields precise predictions wide range interfaces discriminates them from small-molecule sites. Beyond its predictive power, the approach permits dissect interaction surfaces unravel complexity. We show how analysis predicted patches can foster strategies PPIs modulation surface redesign. is JET2, an automated tool based on Joint Evolutionary Trees (JET) sequence-based interface prediction. JET2 freely available at www.lcqb.upmc.fr/JET2.