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A hierarchical approach to protein molecular evolution

Bogarad, Leonard D. and Deem, Michael W. (1999) A hierarchical approach to protein molecular evolution. Proceedings of the National Academy of Sciences of the United States of America, 96 (6). pp. 2591-2595. ISSN 0027-8424. PMCID PMC15812. doi:10.1073/pnas.96.6.2591.

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Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with Monte Carlo simulations. These simulations demonstrate that nonhomologous juxtaposition of encoded structure is the rate-limiting step in the production of new tertiary protein folds. Nonhomologous “swapping” of low-energy secondary structures increased the binding constant of a simulated protein by ≈10^7 relative to base substitution alone. Applications of our approach include the generation of new protein folds and modeling the molecular evolution of disease.

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Additional Information:© 1999 National Academy of Sciences. Communicated by David Chandler, University of California, Berkeley, CA, January 19, 1999 (received for review November 20, 1998). Accepted January 19, 1999. We thank Daan Frenkel and Jonathan Rast for critical readings of our manuscript. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Issue or Number:6
PubMed Central ID:PMC15812
Record Number:CaltechAUTHORS:20141125-154606633
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Official Citation:Leonard D. Bogarad and Michael W. Deem A hierarchical approach to protein molecular evolution PNAS 1999 96 (6) 2591-2595; doi:10.1073/pnas.96.6.2591
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52167
Deposited By: Tony Diaz
Deposited On:26 Nov 2014 00:32
Last Modified:10 Nov 2021 19:22

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