title: Selection on protein structure, interaction, and sequence.
abstract: Characterizing the probabilities of observing amino acid substitutions at specific sites in a protein over evolutionary time is a major goal in the field of molecular evolution. While purely statistical approaches at different levels of complexity exist, approaches rooted in underlying biological processes are necessary to characterize both the context-dependence of sequence changes (epistasis) and to extrapolate to sequences not observed in biological databases. To develop such approaches, an understanding of the different selective forces that act on amino acid substitution is necessary. Here, an overview of selection on and corresponding modeling of folding stability, folding specificity, binding affinity and specificity for ligands, the evolution of new binding sites on protein surfaces, protein dynamics, intrinsic disorder, and protein aggregation as well as the interplay with protein expression level (concentration) and biased mutational processes are presented.
authors.affiliation: Department of Biology and Center for Computational Genetics and Genomics, Temple University, Philadelphia, Pennsylvania, 19122.|Department of Mathematics and Computer Science, Ursinus College, Collegeville, Pennsylvania, 19426.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Chi
authors.affiliation: Department of Biology and Center for Computational Genetics and Genomics, Temple University, Philadelphia, Pennsylvania, 19122.
authors.forename: David A
authors.identifier: 0000-0002-1648-3655
authors.initials: DA
authors.lastname: Liberles
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D019143:Evolution, Molecular; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D011506:Proteins
keywords: mutation-selection models; neutral evolution; protein evolution; sequence-structure-function map