Mohan S, Yathindra N
Department of Crystallography and Biophysics, University of Madras, India.
J Biomol Struct Dyn. 1992 Feb;9(4):695-704. doi: 10.1080/07391102.1992.10507949.
Simultaneous binding of two DAPI molecules in the minor groove of (dA)15.(dT)15 B-DNA helix has been simulated by molecular mechanics calculations. The energy minimised structure shows some novel features in relation to binding of DAPI molecules as well as the flexibility of the grooves of DNA helices. The minor groove of the helix expands locally considerably (to 15 angstroms) to accommodate the two DAPI molecules and is achieved by positive propeller twisting of base pairs at the binding site concomitant with small variations in the local nucleotide stereochemistry. The expansion also brings forth simultaneously a contraction in the width of the major groove spread over to a few phosphates. These findings demonstrate another facet of the flexible stereochemistry of DNA helices in which the local features are significantly altered without being propagated beyond a few base pairs, and with the rest of the regions retaining the normal structure. Both the DAPI molecules are engaged in specific hydrogen bonds with the bases and non specific interactions with phosphates. Stacking interactions of DAPI molecules between themselves as well as with sugar-phosphate backbone contribute to the stability of the complex. The studies provide a stereochemical support to the experimental findings that under high drug-DNA ratio DAPI could bind in the 2:1 ratio.
通过分子力学计算模拟了两个DAPI分子在(dA)15.(dT)15 B - DNA螺旋小沟中的同时结合。能量最小化结构在DAPI分子的结合以及DNA螺旋沟的灵活性方面显示出一些新特征。螺旋的小沟局部显著扩张（至15埃）以容纳两个DAPI分子，这是通过结合位点处碱基对的正向螺旋扭转以及局部核苷酸立体化学的微小变化实现的。这种扩张同时也导致了延伸至几个磷酸基团的大沟宽度的收缩。这些发现展示了DNA螺旋灵活立体化学的另一个方面，即局部特征发生显著改变，但不会传播到几个碱基对之外，其余区域保持正常结构。两个DAPI分子都与碱基形成特定氢键，并与磷酸基团形成非特异性相互作用。DAPI分子之间以及与糖 - 磷酸主链的堆积相互作用有助于复合物的稳定性。这些研究为实验结果提供了立体化学支持，即在高药物 - DNA比例下，DAPI可以以2:1的比例结合。
