Optimization of the CHARMM additive force field for DNA: Improved treatment of the BI/BII conformational equilibrium.
Optimization of the CHARMM additive force field for DNA: Improved treatment of the BI/BII conformational equilibrium.
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DOI：
10.1021/ct200723y
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发表时间：
2012-01-10
影响因子：
5.5
通讯作者：
MacKerell, Alexander D., Jr.
中科院分区：
文献类型：
--
作者：
Hart, Katarina;Foloppe, Nicolas;Baker, Christopher M.;Denning, Elizabeth J.;Nilsson, Lennart;MacKerell, Alexander D., Jr.
DNA的b形式可以填充两种不同的主结构：BI和BII，由扭转角ε和ζ之间的差异定义（BI = ε-ζ < 0和BII = ε-ζ >）。BI是最密集的状态，但BII状态的数量是显著的，它依赖于序列，越来越多的证据表明，BII影响DNA的整体结构，从而影响蛋白质-DNA识别。这项工作提出了CHARMM27加性核酸力场的重新参数化，以增加DNA MD模拟中BII形式的采样。此外，在适当的环境条件下，还引入了糖皱缩的微小修饰，以促进A形式DNA的采样。以模型化合物的量子力学数据为指导进行参数优化，然后对凝聚态的几种DNA双链进行计算。然后，选定的优化参数针对许多DNA双链进行验证，在EcoRI十二聚体上进行了最广泛的测试，包括使用Amber Parm99bsc0力场进行比较计算。新的CHARMM模型更好地再现了实验观察到的BII构象采样，包括采样作为序列的函数。此外，该模型在75%乙醇中再现了1ZF1双相的A形式，并在其晶体环境中产生了稳定的Z-DNA双相构象（GTACGTAC）。最终的模型，结合最近对CHARMM27 RNA力场的重新优化，将被称为CHARMM36。
The B-form of DNA can populate two different backbone conformations: BI and BII, defined by the difference between the torsion angles ε and ζ (BI = ε-ζ < 0 and BII = ε-ζ > 0). BI is the most populated state, but the population of the BII state, which is sequence dependent, is significant and accumulating evidence shows that BII affects the overall structure of DNA, and thus influences protein-DNA recognition. This work presents a reparametrization of the CHARMM27 additive nucleic acid force field to increase the sampling of the BII form in MD simulations of DNA. In addition, minor modifications of sugar puckering were introduced to facilitate sampling of the A form of DNA under the appropriate environmental conditions. Parameter optimization was guided by quantum mechanical data on model compounds, followed by calculations on several DNA duplexes in the condensed phase. The selected optimized parameters were then validated against a number of DNA duplexes, with the most extensive tests performed on the EcoRI dodecamer, including comparative calculations using the Amber Parm99bsc0 force field. The new CHARMM model better reproduces experimentally observed sampling of the BII conformation, including sampling as a function of sequence. In addition, the model reproduces the A form of the 1ZF1 duplex in 75 % ethanol, and yields a stable Z-DNA conformation of duplex (GTACGTAC) in its crystal environment. The resulting model, in combination with a recent reoptimization of the CHARMM27 force field for RNA, will be referred to as CHARMM36.
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影响因子：
15
作者：
ALTONA, C;SUNDARALINGAM, M
通讯作者：
SUNDARALINGAM, M
DOI：
10.1111/j.1432-1033.1993.tb17807.x
发表时间：
1993-04-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
DESTAINTOT, BL;DAUTANT, A;PRECIGOUX, G
通讯作者：
PRECIGOUX, G
影响因子：
3.4
作者：
BERMAN, HM;OLSON, WK;SCHNEIDER, B
通讯作者：
SCHNEIDER, B
影响因子：
3.4
作者：
Foloppe, N;MacKerell, AD
通讯作者：
MacKerell, AD
影响因子：
3.3
作者：
Baker, Christopher M.;Anisimov, Victor M.;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.