DAPI binding to the DNA minor groove: a continuum solvent analysis
DAPI binding to the DNA minor groove: a continuum solvent analysis
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DOI：
10.1002/jmr.581
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发表时间：
2002-07-01
影响因子：
2.7
通讯作者：
Zacharias, M
中科院分区：
文献类型：
--
作者：
De Castro, LFP;Zacharias, M
基于广义Born（GB）或有限差分Poisson-Boltzmann（FDPB）方法的连续溶剂模型已被用于比较4'-6-联脒-2-苯基吲哚（DAPI）与各种DNA序列的小沟的结合。GB和FDPB方法的结果之间以及计算和实验观察到的DAPI与B-DNA结合的序列特异性的趋势之间的定性一致。计算的结合能被分解为溶剂化和DNA-配体相互作用的各种贡献。发现DNA构象适应对计算的总相互作用能做出有利的贡献，但没有改变不同DNA序列的DAPI结合亲和力排名。计算表明，封闭的复合物的形成主要是由非极性的贡献，并被发现是不利的静电由于去溶剂化惩罚，超过有吸引力的库仑相互作用。与富含AT的靶序列相比，DAPI与富含GC的序列结合的计算罚分更大，并且FDPB与GB连续体模型相比通常更大。DAPI在离DNA小沟不同距离处的径向相互作用曲线揭示了离封闭结合几何形状几埃远的静电能最小值。计算出的静电相互作用达到这个距离是有吸引力的，它可以稳定非特异性结合的安排。版权所有（C）2002约翰威利父子有限公司
A continuum solvent model based on the generalized Born (GB) or finite-difference Poisson-Boltzmann (FDPB) approaches has been employed to compare the binding of 4'-6-diamidine-2-phenyl indole (DAPI) to the minor groove of various DNA sequences. Qualitative agreement between the results of GB and FDPB approaches as well as between calculated and experimentally observed trends regarding the sequence specificity of DAPI binding to B-DNA was obtained. Calculated binding energies were decomposed into various contributions to solvation and DNA-ligand interaction. DNA conformational adaptation was found to make a favorable contribution to the calculated total interaction energy but did not change the DAPI binding affinity ranking of different DNA sequences. The calculations indicate that closed complex formation is mainly driven by nonpolar contributions and was found to be disfavored electrostatically due to a desolvation penalty that outbalances the attractive Coulomb interaction. The calculated penalty was larger for DAPI binding to GC-rich sequences compared with AT-rich target sequences and generally larger for the FDPB vs the GB continuum model. A radial interaction profile for DAPI at different distances from the DNA minor groove revealed an electrostatic energy minimum a few Angstroms farther away from the closed binding geometry. The calculated electrostatic interaction up to this distance is attractive and it may stabilize a nonspecific binding arrangement. Copyright (C) 2002 John Wiley Sons, Ltd.