Konerding D E, Cheatham T E, Kollman P A, James T L
University of California, San Francisco 94143, USA.
J Biomol NMR. 1999 Feb;13(2):119-31. doi: 10.1023/a:1008353423074.
Restrained and unrestrained aqueous solution molecular dynamics simulations applying the particle mesh Ewald (PME) method to DNA duplex structures previously determined via in vacuo restrained molecular dynamics with NMR-derived restraints are reported. Without experimental restraints, the DNA decamer, d(CATTTGCATC).d(GATGCAAATG) and trisdecamer, d(AGCTTGCCTTGAG).d(CTCAAGGCAAGCT), structures are stable on the nanosecond time scale and adopt conformations in the B-DNA family. These free DNA simulations exhibit behavior characteristic of PME simulations previously performed on DNA sequences, including a low helical twist, frequent sugar pucker transitions, BI-BII(epsilon-zeta) transitions and coupled crakshaft (alpha-gamma) motion. Refinement protocols similar to the original in vacuo restrained molecular dynamics (RMD) refinements but in aqueous solution using the Cornell et al. force field [Cornell et al. (1995) J. Am. Chem. Soc., 117, 5179-5197] and a particle mesh Ewald treatment produce structures which fit the restraints very well and are very similar to the original in vacuo NMR structure, except for a significant difference in the average helical twist. Figures of merit for the average structure found in the RMD PME decamer simulations in solution are equivalent to the original in vacuo NMR structure while the figures of merit for the free MD simulations are significantly higher. The free MD simulations with the PME method, however, lead to some sequence-dependent structural features in common with the NMR structures, unlike free MD calculations with earlier force fields and protocols. There is some suggestion that the improved handling of electrostatics by PME improves long-range structural aspects which are not well defined by the short-range nature of NMR restraints.
本文报道了采用粒子网格埃瓦尔德（PME）方法对先前通过具有核磁共振（NMR）衍生约束的真空受限分子动力学确定的DNA双链结构进行的受限和无约束水溶液分子动力学模拟。在没有实验约束的情况下，DNA十聚体d（CATTTGCATC）.d（GATGCAAATG）和十三聚体d（AGCTTGCCTTGAG）.d（CTCAAGGCAAGCT）的结构在纳秒时间尺度上是稳定的，并采用B-DNA家族中的构象。这些自由DNA模拟展现出了先前对DNA序列进行的PME模拟的行为特征，包括低螺旋扭转、频繁的糖环构象转变、BI-BII（ε-ζ）转变以及耦合的曲轴（α-γ）运动。类似于原始真空受限分子动力学（RMD）优化，但在水溶液中使用康奈尔等人的力场[康奈尔等人（1995年）《美国化学会志》，117，5179 - 5197]和粒子网格埃瓦尔德处理的优化方案产生的结构与约束非常吻合，并且与原始真空NMR结构非常相似，只是平均螺旋扭转存在显著差异。溶液中RMD PME十聚体模拟中发现的平均结构的品质因数与原始真空NMR结构相当，而自由MD模拟的品质因数则显著更高。然而，与早期力场和方案的自由MD计算不同，采用PME方法的自由MD模拟导致了一些与NMR结构共有的序列依赖性结构特征。有迹象表明，PME对静电的改进处理改善了长程结构方面，而这在NMR约束的短程性质中并未得到很好的定义。
