OPLS POTENTIAL FUNCTIONS FOR NUCLEOTIDE BASES - RELATIVE ASSOCIATION CONSTANTS OF HYDROGEN-BONDED BASE-PAIRS IN CHLOROFORM
OPLS POTENTIAL FUNCTIONS FOR NUCLEOTIDE BASES - RELATIVE ASSOCIATION CONSTANTS OF HYDROGEN-BONDED BASE-PAIRS IN CHLOROFORM
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DOI：
10.1021/ja00008a002
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发表时间：
1991-04-10
影响因子：
15
通讯作者：
JORGENSEN, WL
中科院分区：
文献类型：
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作者：
PRANATA, J;WIERSCHKE, SG;JORGENSEN, WL
通过拟合大量碱基-水复合物的从头计算6-31 G（d）的结果，开发了核苷酸碱基和2，6-二氨基吡啶的OPLS格式的势能函数。 这些潜在的功能产生的偶极矩和碱基对相互作用能与现有的实验数据吻合得很好。 在Monte Carlo模拟中，用统计微扰理论进一步测试势函数，以计算9-甲基鸟嘌呤与1-甲基胞嘧啶（G-C）与9-甲基腺嘌呤与1-甲基尿嘧啶（A-U）以及G-C与1-甲基尿嘧啶与2，6-二氨基吡啶（U-DAP）在氯仿中结合的相对自由能。计算预测G-C复合物比A-U和U-DAP复合物稳定约5 kcal/mol。 类似的稳定性，如A-U和U-DAP复合物的实验观察，虽然在G-C的定量增强似乎被夸大的模拟。 G-C和类似的三重氢键U-DAP之间的缔合常数的巨大差异可追溯到气相相互作用能，这有利于G-C约10千卡/摩尔。 这反过来又是由两种复合物中氢键供体和受体位点的不同排列引起的，这导致了相对于G-C不利于U-DAP的二次静电相互作用。 一般的重要性，这种二次相互作用的理解变化协会进行了讨论。
Potential functions in the OPLS format have been developed for the nucleotide bases and 2,6-diaminopyridine by fitting to the results of ab initio 6-31 G(d) calculations for numerous base-water complexes. These potential functions yield dipole moments and base pair interaction energies in good agreement with available experimental data. The potential functions were tested further in Monte Carlo simulations with statistical perturbation theory to calculate the relative free energies of binding in chloroform for 9-methylguanine with 1-methylcytosine (G-C) versus 9-methyladenine with 1-methyluracil (A-U), and for G-C versus 1-methyluracil with 2,6-diaminopyridine (U-DAP). The calculations predict the G-C complex to be more stable than both the A-U and U-DAP complexes by about 5 kcal/mol. The similar stabilities for complexes like A-U and U-DAP are observed experimentally, though the quantitative enhancement in going to G-C appears to be exaggerated in the simulations. The large difference in association constants between G-C and the similarly triply hydrogen-bonded U-DAP is traced to the gas-phase interaction energies, which favors G-C by about 10 kcal/mol. This in turn is caused by the different arrangement of hydrogen bond donor and acceptor sites in the two complexes, which leads to secondary electrostatic interactions that disfavor U-DAP relative to G-C. The general importance of such secondary interactions for understanding variations in association is discussed.