A computational study of expanded heterocyclic nucleosides in DNA.
A computational study of expanded heterocyclic nucleosides in DNA.
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DOI：
10.1080/07391102.2008.10507243
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发表时间：
2008-12
影响因子：
4.4
通讯作者：
Seley-Radtke, Katherine L.
中科院分区：
文献类型：
--
作者：
O'Daniel, Peter I.;Jefferson, Malcolm;Wiest, Olaf;Seley-Radtke, Katherine L.
首次在AMBER中利用修正的力场参数对DNA中一系列异间隔基扩展的三环碱基进行了分子动力学研究。已设计扩展嘌呤核苷单体来探测杂芳族间隔环对DNA螺旋的结构、功能和动力学的影响。杂碱基支架已经用呋喃、吡咯或噻吩间隔环扩展。这种结构修饰增加了碱的极化率，并提供了具有吡咯环的胺氢的额外氢键供体或具有呋喃或噻吩环自由电子对的氢键受体。通过AM 1计算确定了扩展的碱基的极化率，并且20-mer的MD模拟的结果预测，扩展的碱基的修改的曲率导致大得多的大沟，而对小沟的影响可以忽略不计。总的来说，结构类似于A-DNA。10-mer的MD模拟表明，碱基配对与碱基堆叠和插入之间的平衡可以向后者转移，由于扩大的碱基的表面积和极化能力的增加。
The first molecular dynamics study of a series of heterospacer-expanded tricyclic bases in DNA using modified force field parameters in AMBER is detailed. The expanded purine nucleoside monomers have been designed to probe the effects of a heteroaromatic spacer ring on the structure, function, and dynamics of the DNA helix. The heterobase scaffold has been expanded with a furan, pyrrole, or thiophene spacer ring. This structural modification increases the polarizability of the bases and provides an additional hydrogen bond donor with the amine hydrogen of the pyrrole ring or hydrogen bond acceptor with the furan or thiophene ring free electron pairs. The polarizability of the expanded bases were determined by AM1 calculations and the results of the MD simulations of 20-mers predict that the modified curvature of the expanded base leads to a much larger major groove, while the effect on the minor groove is negligible. Overall, the structure resembles A-DNA. MD simulations of 10-mers suggest that the balance between base pairing vs. base stacking and intercalation can be shifted towards the latter due to the increased surface area and polariz-ability of the expanded bases.
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影响因子：
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