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Sampling realistic protein conformations using local structural bias.

ABSTRACT: 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.

SUBMITTER: Hamelryck T

PROVIDER: S-EPMC1570370 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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Sampling realistic protein conformations using local structural bias.

Hamelryck Thomas T Kent John T JT Krogh Anders A

PLoS computational biology 20060821 9

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, nati ...[more]

PMID: 17002495

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Sampling realistic protein conformations using local structural bias.

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Sampling realistic protein conformations using local structural bias.

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