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Genes 2011, 2(4), 748-762; doi:10.3390/genes2040748

The Evolution of Protein Structures and Structural Ensembles Under Functional Constraint

Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA
Authors to whom correspondence should be addressed.
Received: 24 September 2011 / Revised: 15 October 2011 / Accepted: 19 October 2011 / Published: 28 October 2011
(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes 2011)
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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 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. View Full-Text
Keywords: conformational ensemble; multiscale modeling; structural disorder; sequence-structure-function-evolution relationships conformational ensemble; multiscale modeling; structural disorder; sequence-structure-function-evolution relationships

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

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.

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