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Sampling Realistic Protein Conformations Using Local Structural Bias

Hamelryck, T., Kent, J.T. and Krogh, A. (2006) Sampling Realistic Protein Conformations Using Local Structural Bias. PLoS Computational Biology, 2 (9). e131. ISSN 1553-734X


The prediction of protein structure from sequence remains a major unsolved problem in biology. The most successful protein structure prediction methods make use of a divide-and-conquer strategy to attack the problem: a conformational sampling method generates plausible candidate structures, which are subsequently accepted or rejected using an energy function. Conceptually, this often corresponds to separating local structural bias from the long-range interactions that stabilize the compact, native state. However, sampling protein conformations that are compatible with the local structural bias encoded in a given protein sequence is a long-standing open problem, especially in continuous space. We describe an elegant and mathematically rigorous method to do this, and show that it readily generates native-like protein conformations simply by enforcing compactness. Our results have far-reaching implications for protein structure prediction, determination, simulation, and design.

Item Type: Article
Copyright, Publisher and Additional Information: © 2006 Hamelryck et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institution: The University of Leeds
Academic Units: The University of Leeds > Faculty of Maths and Physical Sciences (Leeds) > School of Mathematics (Leeds) > Statistics (Leeds)
Depositing User: Sherpa Assistant
Date Deposited: 06 Nov 2009 12:07
Last Modified: 26 Jun 2014 04:26
Published Version: http://dx.doi.org/10.1371/journal.pcbi.0020131
Status: Published
Publisher: Public Library of Science
Identification Number: 10.1371/journal.pcbi.0020131
URI: http://eprints.whiterose.ac.uk/id/eprint/10104

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