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Atomistic modeling of protein-DNA interaction specificity: progress and applications.

ABSTRACT: An accurate, predictive understanding of protein-DNA binding specificity is crucial for the successful design and engineering of novel protein-DNA binding complexes. In this review, we summarize recent studies that use atomistic representations of interfaces to predict protein-DNA binding specificity computationally. Although methods with limited structural flexibility have proven successful at recapitulating consensus binding sequences from wild-type complex structures, conformational flexibility is likely important for design and template-based modeling, where non-native conformations need to be sampled and accurately scored. A successful application of such computational modeling techniques in the construction of the TAL-DNA complex structure is discussed. With continued improvements in energy functions, solvation models, and conformational sampling, we are optimistic that reliable and large-scale protein-DNA binding prediction and engineering is a goal within reach.

SUBMITTER: Liu LA

PROVIDER: S-EPMC3425445 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Atomistic modeling of protein-DNA interaction specificity: progress and applications.

Liu Limin Angela LA Bradley Philip P

Current opinion in structural biology 20120713 4

An accurate, predictive understanding of protein-DNA binding specificity is crucial for the successful design and engineering of novel protein-DNA binding complexes. In this review, we summarize recent studies that use atomistic representations of interfaces to predict protein-DNA binding specificity computationally. Although methods with limited structural flexibility have proven successful at recapitulating consensus binding sequences from wild-type complex structures, conformational flexibili ...[more]

PMID: 22796087

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