Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Curr Opin Struct Biol. 2012 Aug;22(4):397-405. doi: 10.1016/j.sbi.2012.06.002. Epub 2012 Jul 13.
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.
准确、可预测的蛋白质-DNA 结合特异性理解对于新型蛋白质-DNA 结合复合物的成功设计和工程至关重要。在这篇综述中，我们总结了最近使用界面的原子表示来计算预测蛋白质-DNA 结合特异性的研究。尽管具有有限结构灵活性的方法已被证明成功地从野生型复合物结构中重现了共识结合序列，但构象灵活性对于设计和基于模板的建模可能很重要，其中需要采样和准确评分非天然构象。讨论了这种计算建模技术在 TAL-DNA 复合物结构构建中的成功应用。随着能量函数、溶剂模型和构象采样的不断改进，我们乐观地认为可靠和大规模的蛋白质-DNA 结合预测和工程是一个可行的目标。
