the evolution of protein structures and structural ensembles under functional constraint蛋白质结构的进化和结构功能约束下集合体.pdf

Genes 2011, 2, 748-762; doi:10.3390/genes2040748 OPEN ACCESS genes ISSN 2073-4425 /journal/genes Review The Evolution of Protein Structures and Structural Ensembles Under Functional Constraint Jessica Siltberg-Liberles *, Johan A. Grahnen and David A. Liberles * Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA; E-Mail: jgrahnen@ * Author to whom correspondence should be addressed; E-Mails: jliberle@ (J.S.-L.); liberles@ (D.A.L.). Received: 24 September 2011; in revised form: 15 October 2011 / Accepted: 19 October 2011 / Published: 28 October 2011 Abstract: Protein sequence, structure, and function are inherently linked through evolution and population genetics. Our knowledge of protein structure comes from solved structures in the Protein Data Bank (PDB), our knowledge of sequence through sequences found in the NCBI sequence databases (/), and our knowledge of function through a limited set of in-vitro biochemical studies. How these intersect through evolution is described in the first part of the review. In the second part, our understanding of a series of questions is addressed. This includes how sequences evolve within structures, how evolutionary processes enable structural transitions, how the folding process can change through evolution and what the fitness impacts of this might be. Moving beyond static structures, the evolution of protein kinetics (including normal modes) is discussed, as is the evolution of conformationa