Reddy C K, Das A, Jayaram B
Department of Chemistry, Indian Institute of Technology, New Delhi, Hauz Khas, 110016, India.
J Mol Biol. 2001 Nov 30;314(3):619-32. doi: 10.1006/jmbi.2001.5154.
A comprehensive analysis of interfacial water molecules in the structures of 109 unique protein-DNA complexes is presented together with a new view on their role in protein-DNA recognition. Location of interfacial water molecules as reported in the crystal structures and as emerging from a series of molecular dynamics studies on protein-DNA complexes with explicit solvent and counterions, was analyzed based on their acceptor, donor hydrogen bond relationships with the atoms and residues of the macromolecules, electrostatic field calculations and packing density considerations. Water molecules for the purpose of this study have been categorized into four classes: viz. (I) those that contact both the protein and the DNA simultaneously and thus mediate recognition directly; (II) those that contact either the protein or the DNA exclusively via hydrogen bonds solvating each solute separately; (III) those that contact the hydrophobic groups in either the protein or the DNA; and, lastly (IV) those that contact another water molecule. Of the 17,963 crystallographic water molecules under examination, about 6% belong to class I and 76% belong to class II. About three-fourths of class I and class II water molecules are exclusively associated with hydrogen bond acceptor atoms of both protein and DNA. Noting that DNA is polyanionic, it is significant that a majority of the crystallographically observed water molecules as well as those from molecular dynamics simulations should be involved in facilitating binding by screening unfavorable electrostatics. Less than 2% of the reported water molecules occur between hydrogen bond donor atoms of protein and acceptor atoms of DNA. These represent cases where protein atoms cannot reach out to DNA to make favorable hydrogen bond interactions due to packing/structural restrictions and interfacial water molecules provide an extension to side-chains to accomplish hydrogen bonding.
本文对109种独特蛋白质-DNA复合物结构中的界面水分子进行了全面分析，并对其在蛋白质-DNA识别中的作用提出了新观点。基于界面水分子与大分子原子和残基的受体、供体氢键关系、静电场计算和堆积密度考虑，分析了晶体结构中报道的以及一系列含有明确溶剂和抗衡离子的蛋白质-DNA复合物分子动力学研究中出现的界面水分子位置。为了本研究的目的，水分子被分为四类：即（I）那些同时接触蛋白质和DNA并因此直接介导识别的水分子；（II）那些仅通过氢键分别溶剂化每种溶质而接触蛋白质或DNA的水分子；（III）那些接触蛋白质或DNA中疏水基团的水分子；最后（IV）那些接触另一个水分子的水分子。在所研究的17963个晶体学水分子中，约6%属于I类，76%属于II类。I类和II类水分子中约四分之三仅与蛋白质和DNA的氢键受体原子相关。注意到DNA是多阴离子的，重要的是，晶体学观察到的大多数水分子以及分子动力学模拟中的水分子应通过筛选不利的静电作用来促进结合。报道的水分子中不到2%出现在蛋白质的氢键供体原子和DNA的受体原子之间。这些代表了由于堆积/结构限制蛋白质原子无法与DNA形成有利氢键相互作用的情况，而界面水分子为侧链提供了延伸以完成氢键形成。
