Subramanian P S, Pitchumani S, Beveridge D L, Berman H M
Chemistry Department, Wesleyan University, Middletown, Connecticut 06457.
Biopolymers. 1990 Mar-Apr;29(4-5):771-83. doi: 10.1002/bip.360290411.
Monte Carlo computer simulation is described for the dinucleotide duplex rGpC together with 562 water molecules at an environmental density of 1 g/cc in a cubic cell under periodic boundary conditions. Water-water interactions were treated using the TIP4P potential and the solute water interactions by TIP4P spliced with the nonbonded interactions from the AMBER 3.0 force field. The simulation was subjected to proximity analysis to obtain solute coordinate numbers and pair interaction energies for each solute atom. Hydration density distributions partitioned into contributions from the major groove side, the minor groove side and the sugar-phosphate backbone were examined, and the probabilities of occurrence for one- and two-water bridges in the simulation were enumerated. The results were compared with observations of crystallographic ordered water sites from x-ray diffraction studies on G and C containing small molecules, and in crystal structure determinations of the sodium, calcium, and ammonium salts of rGpC. The calculated results are generally consistent with the observed sites, except for cytosine N4, where a hydration site is predicted yet none observed in rGpC salts, and for guanine N3, which appears in this calculation to compete unfavorably with the adjacent donor site at guanine N2. There is, however, a significant probability of finding a one-water G-N3-W-G-N2 bridge indicated in the simulation. An explanation for the guanine N3 discrepancy in terms of electrostatic potentials is also offered. The calculated one- and two-water bridges in the rGpC hydration complex coincide in a number of cases to those observed in the ordered water structure of the sodium rGpC crystal hydrate.
描述了对含有562个水分子的二核苷酸双链体rGpC进行的蒙特卡罗计算机模拟。该模拟在周期性边界条件下，于一个立方晶胞中，环境密度为1 g/cc的条件下进行。水-水相互作用采用TIP4P势处理，溶质-水相互作用则通过将TIP4P与来自AMBER 3.0力场的非键相互作用拼接来处理。对模拟结果进行邻近分析，以获得每个溶质原子的溶质配位数和对相互作用能。研究了水合密度分布，将其划分为来自大沟侧、小沟侧和糖-磷酸主链的贡献，并列举了模拟中一水桥和二水桥出现的概率。将结果与对含G和C的小分子进行X射线衍射研究以及rGpC的钠、钙和铵盐晶体结构测定中晶体学有序水位点的观测结果进行了比较。计算结果与观测位点总体一致，但胞嘧啶N4除外，在rGpC盐中预测有一个水合位点但未观测到；鸟嘌呤N3也除外，在此计算中它与鸟嘌呤N2处相邻的供体位点竞争不利。然而，在模拟中发现存在一个一水G-N3-W-G-N2桥的可能性很大。还从静电势的角度对鸟嘌呤N3的差异给出了解释。rGpC水合复合物中计算得到的一水桥和二水桥在许多情况下与钠rGpC晶体水合物有序水结构中观测到的一致。
