title: Evolution of off-lattice model proteins under ligand binding constraints.
abstract: We investigate protein evolution using an off-lattice polymer model evolved to imitate the behavior of small enzymes. Model proteins evolve through mutations to nucleotide sequences (including insertions and deletions) and are selected to fold and maintain a specific binding site compatible with a model ligand. We show that this requirement is, in itself, sufficient to maintain an ordered folding domain, and we compare it to the requirement of folding an ordered (but otherwise unrestricted) domain. We measure rates of amino acid change as a function of local environment properties such as solvent exposure, packing density, and distance from the active site, as well as overall rates of sequence and structure change, both along and among model lineages in star phylogenies. The model recapitulates essentially all of the behavior found in protein phylogenetic analyses, and predicts that amino acid substitution rates vary linearly with distance from the binding site.
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Blvd., Room ND10.124, Dallas, Texas 75235-9050, USA.
authors.forename: Erik D
authors.initials: ED
authors.lastname: Nelson
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Blvd., Room ND10.124, Dallas, Texas 75235-9050, USA.
authors.forename: Nick V
authors.initials: NV
authors.lastname: Grishin
mesh_terms: D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D008024:Ligands; D009154:Mutation; D010802:Phylogeny; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D008024:Ligands; D011506:Proteins