a combinatorial approach to detect coevolved amino acid networks in protein families of variable divergence组合的方法来检测蛋白质氨基酸网络协同进化的家庭变量散度.pdfVIP

A Combinatorial Approach to Detect Coevolved Amino Acid Networks in Protein Families of Variable Divergence Julie Baussand1,2, Alessandra Carbone1,2* ´ ´ ´ 1 Genomique Analytique, Universite Pierre et Marie Curie, Paris, France, 2 Genomique des Microorganismes, CNRS, Paris, France Abstract Communication between distant sites often defines the biological role of a protein: amino acid long-range interactions are as important in binding specificity, allosteric regulation and conformational change as residues directly contacting the substrate. The maintaining of functional and structural coupling of long-range interacting residues requires coevolution of these residues. Networks of interaction between coevolved residues can be reconstructed, and from the networks, one can possibly derive insights into functional mechanisms for the protein family. We propose a combinatorial method for mapping conserved networks of amino acid interactions in a protein which is based on the analysis of a set of aligned sequences, the associated distance tree and the combinatorics of its subtrees. The degree of coevolution of all pairs of coevolved residues is identified numerically, and networks are reconstructed with a dedicated clustering algorithm. The method drops the constraints on high sequence divergence limiting the range of applicability of the statistical approaches previously proposed. We apply the method to four protein families where we show an accurate detection of functional networks and the possibility to treat sets of protein sequences of variable divergence. Citation: Baussand J, Carbone A (2009) A Combinatorial Approach to Detect Coevolved Amino Acid Networks in Protein Families of Variable Divergence. PLoS Comput Biol