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The Evolution of Protein Structures and Structural Ensembles Under Functional Constraint
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA
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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 (http://www.ncbi.nlm.nih.gov/), 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 conformational ensembles and structurally disordered proteins. This ties back to a question of the role of neostructuralization and how it relates to selection on sequences for functions. The relationship between metastability, the fitness landscape, sequence divergence, and organismal effective population size is explored. Lastly, a brief discussion of modeling the evolution of sequences of ordered and disordered proteins is entertained.
Keywords: conformational ensemble; multiscale modeling; structural disorder; sequence-structure-function-evolution relationships
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Siltberg-Liberles, J.; Grahnen, J.A.; Liberles, D.A. The Evolution of Protein Structures and Structural Ensembles Under Functional Constraint. Genes 2011, 2, 748-762.
Siltberg-Liberles J, Grahnen JA, Liberles DA. The Evolution of Protein Structures and Structural Ensembles Under Functional Constraint. Genes. 2011; 2(4):748-762.
Siltberg-Liberles, Jessica; Grahnen, Johan A.; Liberles, David A. 2011. "The Evolution of Protein Structures and Structural Ensembles Under Functional Constraint." Genes 2, no. 4: 748-762.