title: The Role of Evolutionary Selection in the Dynamics of Protein Structure Evolution.
abstract: Homology modeling is a powerful tool for predicting a protein's structure. This approach is successful because proteins whose sequences are only 30% identical still adopt the same structure, while structure similarity rapidly deteriorates beyond the 30% threshold. By studying the divergence of protein structure as sequence evolves in real proteins and in evolutionary simulations, we show that this nonlinear sequence-structure relationship emerges as a result of selection for protein folding stability in divergent evolution. Fitness constraints prevent the emergence of unstable protein evolutionary intermediates, thereby enforcing evolutionary paths that preserve protein structure despite broad sequence divergence. However, on longer timescales, evolution is punctuated by rare events where the fitness barriers obstructing structure evolution are overcome and discovery of new structures occurs. We outline biophysical and evolutionary rationale for broad variation in protein family sizes, prevalence of compact structures among ancient proteins, and more rapid structure evolution of proteins with lower packing density.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
authors.forename: Amy I
authors.initials: AI
authors.lastname: Gilson
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
authors.forename: Ahmee
authors.initials: A
authors.lastname: Marshall-Christensen
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
authors.forename: Jeong-Mo
authors.initials: JM
authors.lastname: Choi
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts. Electronic address: shakhnovich@chemistry.harvard.edu.
authors.forename: Eugene I
authors.initials: EI
authors.lastname: Shakhnovich
mesh_terms: D003198:Computer Simulation; D019143:Evolution, Molecular; D008958:Models, Molecular; D009010:Monte Carlo Method; D000072417:Protein Domains; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012641:Selection, Genetic; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins