title: Biophysics of protein evolution and evolutionary protein biophysics.
abstract: The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence-structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by 'hidden' conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution.
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8 Department of Physics, University of Toronto, Toronto, Ontario, Canada M5S 1A8 t.sikosek@utoronto.ca.
authors.forename: Tobias
authors.identifier: http://orcid.org/0000-0001-9929-3525
authors.initials: T
authors.lastname: Sikosek
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8 Department of Physics, University of Toronto, Toronto, Ontario, Canada M5S 1A8 chan@arrhenius.med.toronto.edu.
authors.forename: Hue Sun
authors.initials: HS
authors.lastname: Chan
mesh_terms: D019143:Evolution, Molecular; D017510:Protein Folding; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D011506:Proteins
keywords: adaptation; conformational dynamics; hidden states; promiscuous functions; protein folding; protein–protein interactions