Revealing evolutionary constraints on proteins through sequence analysis

Abstract

Alignments of large numbers of protein sequences have revealed \"sectors\" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any relevant physical property of a protein, e.g. the elastic energy of an important conformational change, can give rise to such a sector. We demonstrate that the main signature of these physical sectors lies in the smalleigenvalue modes of the covariance matrix of the selected sequences. This simple, generic model leads us to propose a principled method to identify sectors, along with the magnitudes of mutational effects, from sequence data.