Co-evolution and interactions within and between proteins – CoevolInterProt

How to represent and understand the couplings between amino acids within and between proteins? We previously analyzed this question in the context of individual proteins. We showed that a protein could comprise different groups of amino acids that co-evolve relatively independently, and are associated with distinct functional properties. These groups of residues, which we call “sectors”, are identified computationally by analyzing statistically multiple sequence alignments, and their functional properties were confirmed experimentally. We propose here to extend this work to the case of inter-protein interactions by analyzing two systems: (1) a system of different enzymes involved in a common metabolic pathway, and (2) antibodies and, more particularly, their binding properties. In the first case, we will seek to derive a description of the functional interactions between enzymes based on our concept of sectors. In the second case, we will analyze the nature and origin of the couplings between amino acids responsible for the specificity of antibodies by taking advantage of a technique of directed evolution by which an evolutionary process can be experimentally simulated.