Atomistic modeling of protein-DNA interaction specificity: progress and applications.
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.
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Limin Angela
LA
Liu
Philip
P
Bradley
D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D051188:Knowledge Bases; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering; D040681:Structural Homology, Protein; D013816:Thermodynamics
D004268:DNA-Binding Proteins; D004247:DNA