Jakubec Dávid, Hostas Jirí, Laskowski Roman A, Hobza Pavel, Vondrásek Jirí
J Chem Theory Comput. 2015 Apr 14;11(4):1939-48. doi: 10.1021/ct501168n.
The growing number of high-quality experimental (X-ray, NMR) structures of protein–DNA complexes has sufficient enough information to assess whether universal rules governing the DNA sequence recognition process apply. While previous studies have investigated the relative abundance of various modes of amino acid–base contacts (van der Waals contacts, hydrogen bonds), relatively little is known about the energetics of these noncovalent interactions. In the present study, we have performed the first large-scale quantitative assessment of binding preferences in protein–DNA complexes by calculating the interaction energies in all 80 possible amino acid–DNA base combinations. We found that several mutual amino acid–base orientations featuring bidentate hydrogen bonds capable of unambiguous one-to-one recognition correspond to unique minima in the potential energy space of the amino acid–base pairs. A clustering algorithm revealed that these contacts form a spatially well-defined group offering relatively little conformational freedom. Various molecular mechanics force field and DFT-D ab initio calculations were performed, yielding similar results.
越来越多高质量的蛋白质 - DNA复合物实验（X射线、核磁共振）结构拥有足够的信息来评估支配DNA序列识别过程的通用规则是否适用。虽然先前的研究已经调查了各种氨基酸 - 碱基接触模式（范德华接触、氢键）的相对丰度，但对于这些非共价相互作用的能量学了解相对较少。在本研究中，我们通过计算所有80种可能的氨基酸 - DNA碱基组合中的相互作用能，首次对蛋白质 - DNA复合物中的结合偏好进行了大规模定量评估。我们发现，几种具有双齿氢键且能够进行明确一对一识别的相互氨基酸 - 碱基取向对应于氨基酸 - 碱基对势能空间中的独特最小值。一种聚类算法表明，这些接触形成了一个空间定义明确的组，提供的构象自由度相对较小。进行了各种分子力学力场和DFT-D从头算计算，得到了相似的结果。
