Structural modeling and design of protein interactions using evolution.

Protein-protein interactions are of fundamental importance in virtually all cellular processes. Our group has focused on the analysis and prediction of these interactions through the combined use of structural data and evolutionary information. In a study of over 1,000 couples of homologous interfaces, we uncovered astonishing plasticity in the way interface structure evolves. We also identified some rather invariant features which provide tracks for extracting meaningful information from multiple sequence alignments of binding partners. On these bases, we developed a protein docking method which improves the prediction of protein interfaces and was used in a number of protein docking cases related to the maintenance of genome stability. Understanding how interfaces co-evolve opens new perspectives for the design of novel protein binders which we shall also discussed.