title: Evolution-Based Functional Decomposition of Proteins.
abstract: The essential biological properties of proteins-folding, biochemical activities, and the capacity to adapt-arise from the global pattern of interactions between amino acid residues. The statistical coupling analysis (SCA) is an approach to defining this pattern that involves the study of amino acid coevolution in an ensemble of sequences comprising a protein family. This approach indicates a functional architecture within proteins in which the basic units are coupled networks of amino acids termed sectors. This evolution-based decomposition has potential for new understandings of the structural basis for protein function. To facilitate its usage, we present here the principles and practice of the SCA and introduce new methods for sector analysis in a python-based software package (pySCA). We show that the pattern of amino acid interactions within sectors is linked to the divergence of functional lineages in a multiple sequence alignment-a model for how sector properties might be differentially tuned in members of a protein family. This work provides new tools for studying proteins and for generally testing the concept of sectors as the principal units of function and adaptive variation.
authors.affiliation: Laboratoire Interdisciplinaire de Physique, CNRS and Université Grenoble Alpes, Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rivoire
authors.affiliation: The Green Center for Systems Biology, and Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Reynolds
authors.affiliation: The Green Center for Systems Biology, and Departments of Biophysics and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Rama
authors.initials: R
authors.lastname: Ranganathan
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000648:ultrastructure; D008956:Models, Chemical; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D019204:GTP-Binding Proteins