title: On the role of physics and evolution in dictating protein structure and function.
abstract: How many of the structural and functional properties of proteins are inherent? Computer simulations provide a powerful tool to address this question. A series of studies on QS, quasi-spherical, compact polypeptides which lack any secondary structure; ART, artificial, proteins comprised of compact homopolypeptides with protein-like secondary structure; and PDB, native, single domain proteins shows that essentially all native global folds, pockets and protein-protein interfaces are in the ART library. This suggests that many protein properties are inherent and that evolution is involved in fine-tuning. The completeness of the space of ligand binding pockets and protein-protein interfaces suggests that promiscuous interactions are intrinsic to proteins and that the capacity to perform the biochemistry of life at low level does not require evolution. If so, this has profound consequences for the origin of life.
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street NW, Atlanta, GA 30318, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skolnick
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street NW, Atlanta, GA 30318, USA.
authors.forename: Mu
authors.initials: M
authors.lastname: Gao
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street NW, Atlanta, GA 30318, USA.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhou
keywords: Completeness of the space of single domain protein structures; ligand binding sites and protein-protein interfaces; origin of protein biochemical function, protein-ligand interactions; promiscuous interactions