Feuerstein B G, Pattabiraman N, Marton L J
Department of Laboratory Medicine, University of California, San Francisco 94143.
Nucleic Acids Res. 1989 Sep 12;17(17):6883-92. doi: 10.1093/nar/17.17.6883.
We used molecular dynamics to model interactions between the physiologically important polyamine spermine and two B-DNA oligomers, the homopolymer (dG)10-(dC)10 and the heteropolymer (dGdC)5-(dGdC)5. Water and counterions were included in the simulation. Starting coordinates for spermine-DNA complexes were structures obtained by molecular mechanics modeling of spermine with the two oligomers; in these models, spermine binding induced a bend in the heteropolymer but not in the homopolymer. During approximately 40 psec of molecular dynamics simulation, spermine moves away from the floor of the major groove and interacts nospecifically with d(G)10-d(C)10. In contrast, a spermine-induced bend in the helix of (dGdC)5-(dGdC)5 is maintained throughout the simulation and spermine remains closely associated with the major groove. These results provide further evidence that the binding of spermine to nucleic acids can be sequence specific and that bending of alternating purine-pyrimidine sequences may be a physiologically important result of spermine binding.
我们利用分子动力学对生理上重要的多胺精胺与两种B - DNA寡聚物（同聚物(dG)10-(dC)10和杂聚物(dGdC)5-(dGdC)5）之间的相互作用进行建模。模拟中包含了水和抗衡离子。精胺 - DNA复合物的起始坐标是通过精胺与这两种寡聚物的分子力学建模得到的结构；在这些模型中，精胺结合使杂聚物发生弯曲，但同聚物未发生弯曲。在大约40皮秒的分子动力学模拟过程中，精胺从大沟底部移开，并与d(G)10 - d(C)10发生非特异性相互作用。相比之下，在整个模拟过程中，(dGdC)5-(dGdC)5螺旋中由精胺诱导的弯曲得以维持，并且精胺与大沟保持紧密结合。这些结果进一步证明精胺与核酸的结合可能具有序列特异性，并且交替嘌呤 - 嘧啶序列的弯曲可能是精胺结合的一个重要生理结果。
