Local and global effects of strong DNA bending induced during molecular dynamics simulations
Local and global effects of strong DNA bending induced during molecular dynamics simulations
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DOI：
10.1093/nar/gkp234
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发表时间：
2009-06-01
影响因子：
14.9
通讯作者：
Zakrzewska, Krystyna
中科院分区：
文献类型：
--
作者：
Curuksu, Jeremy;Zacharias, Martin;Zakrzewska, Krystyna
DNA弯曲在许多生物过程中起着重要的作用，但其分子和能量细节作为碱基序列的函数仍有待充分理解。使用最近开发的约束，我们已经研究了四个不同的B-DNA寡聚体的分子动力学模拟的控制弯曲。用AMBER程序和最近的parmbsc 0力场进行伞式取样，得到弯曲的自由能曲线。将15个碱基对的寡聚体弯曲90 °需要大约5 kcalmol（1），而达到150 °需要12 kcalmol（1）的数量级。中度弯曲主要通过耦合的基对阶梯辊发生。强烈的弯曲通常会导致局部扭结。我们观察到的扭结都涉及两个连续的碱基对步骤，与中断的中心碱基对（在早期的工作称为II型扭结）。对每种低聚物的详细分析表明，对于中等弯曲，弯曲自由能仅随弯曲角度呈二次方变化。超过这一点，与最近的实验一致，变化变成线性的。每个基本步骤的谐波分析产生的力常数，不仅随顺序，而且与弯曲的程度。这两个观察结果都表明，DNA在机械上比简单的弹性杆模型所暗示的要复杂得多。
DNA bending plays an important role in many biological processes, but its molecular and energetic details as a function of base sequence remain to be fully understood. Using a recently developed restraint, we have studied the controlled bending of four different B-DNA oligomers using molecular dynamics simulations. Umbrella sampling with the AMBER program and the recent parmbsc0 force field yield free energy curves for bending. Bending 15-base pair oligomers by 90 requires roughly 5kcalmol(1), while reaching 150 requires of the order of 12kcalmol(1). Moderate bending occurs mainly through coupled base pair step rolls. Strong bending generally leads to local kinks. The kinks we observe all involve two consecutive base pair steps, with disruption of the central base pair (termed Type II kinks in earlier work). A detailed analysis of each oligomer shows that the free energy of bending only varies quadratically with the bending angle for moderate bending. Beyond this point, in agreement with recent experiments, the variation becomes linear. An harmonic analysis of each base step yields force constants that not only vary with sequence, but also with the degree of bending. Both these observations suggest that DNA is mechanically more complex than simple elastic rod models would imply.