Complexity Forum

Title: Inference of protein-protein interactions from multi-species sequence data using statistical-physics inspired approaches

Abstract:

Experimental approaches to transient protein interactions are laborious and serendipitous, and our understanding of fundamental questions like the identification of interaction surfaces or the specificity of molecular recognition between interacting proteins are far from being solved. We propose a computational approach based on recent techniques from the statistical physics of disordered systems, which exploits the natural sequence variability of homologous proteins across hundreds of species species. Using bacterial two-component signal transduction (TCS) as a test case, we show that our method is able (i) to identify inter-protein residue contacts and to facilitate the prediction of protein complex strutures, and (ii) to reconstruct a molecular recognition code which elucidates specificity in signal transduction in bacteria.

[M. Weigt, R.A. White, H. Szurmant, J.A. Hoch, T. Hwa, "Identification of direct residue contacts in protein-protein interaction by message passing", Proc. Natl. Acad. Sci. 106, 67 (2009).]