Haworth I S, Elcock A H, Rodger A, Richards W G
Physical Chemistry Laboratory, Oxford, England.
J Biomol Struct Dyn. 1991 Dec;9(3):553-69. doi: 10.1080/07391102.1991.10507936.
Molecular mechanics calculations and molecular dynamics simulations have been used to study the binding of the partially inserted major groove complex of Lambda-[Ru(1,10-phenanthroline)3]2+ with DNA. Energy refinements of this complex showed a clear preference for binding at purine-3',5'-pyrimidine sites over pyrimidine-3',5'-purine sites. The basis for this difference is shown to be a slight change in the binding orientation induced by interchanging the purine and pyrimidine bases. This in turn provides for a better secondary interaction with the helix backbone at a point beyond the immediate binding site. It is this secondary interaction that provides the additional energetic stabilisation for complexes formed at purine-3',5'-pyrimidine sites. Molecular dynamics simulations including explicit representation of solvent support these conclusions and provide an insight into the positional stability of the ligand at a particular site. Repuckering of specific deoxyribose rings to the C3'-endo conformation seems to be an important feature of the DNA/ligand complex.
分子力学计算和分子动力学模拟已被用于研究λ-[Ru(1,10-菲咯啉)3]2+与DNA部分插入的大沟复合物的结合。该复合物的能量优化显示，与嘧啶-3',5'-嘌呤位点相比，其在嘌呤-3',5'-嘧啶位点的结合具有明显偏好。这种差异的基础被证明是嘌呤和嘧啶碱基互换所引起的结合方向的轻微变化。这反过来又在紧邻结合位点之外的一点上与螺旋骨架形成了更好的二级相互作用。正是这种二级相互作用为在嘌呤-3',5'-嘧啶位点形成的复合物提供了额外的能量稳定作用。包括明确表示溶剂的分子动力学模拟支持了这些结论，并提供了对配体在特定位点的位置稳定性的深入了解。特定脱氧核糖环重新卷曲为C3'-内向构象似乎是DNA/配体复合物的一个重要特征。
