Fritsch V, Ravishanker G, Beveridge D L, Westhof E
Institut de Biologie Molećulaire et Cellaire du CNRS, Cedex, France.
Biopolymers. 1993 Oct;33(10):1537-52. doi: 10.1002/bip.360331005.
The program AMBER 3.0 has been used to generate molecular dynamics trajectories of a poly(dA).poly(dT) decamer. The simulations were performed using different methods to treat solvent effects. Results of a simulation including 18 counterions NH4+ and 4109 water molecules under (N, P, T) conditions were compared to simulation runs with implicit solvent representation in which solvent screening effects were represented by the use of a sigmoidal distance-dependent dielectric function. In the latter case, the system was simulated under microcanonical (N, V, E) and canonical (N, V, T) conditions. For the fully hydrated system simulation, a preequilibration protocol was developed since it was observed that long and progressive periods of heating and equilibration on the overall system were necessary in order to avoid energetic collisions between the solute and the solvent molecules, leading to severe irreversible deformation of the solute. A detailed analysis of DNA conformations, sugar puckers, and stability of the hydrogen bonds, Watson-Crick and three-center H bonds, is reported. The results show that DNA remains essentially in the B conformer with a tendency in the hydrated model to adopt a slightly distorted, unwound, and stretched conformation in comparison to standard B-DNA. Concerning sugar puckers, the mean pseudorotation phases of the adenine residues are systematically higher than those of the thymine residues, except in the case of the hydrated model for which a articular behavior is observed for the adenine strand. In this case, the terminal bases oscillate between C2'-endo and O4'-endo and the central ones stay in the C3'-endo domain. The mean lifetimes of the internal Watson-Crick H-bond (A) HN6...O4(T) are also dependent on the base pairs included in the calculation, excepted for the implicit solvent simulation at constant temperature. The three-center H bonds have very small mean lifetimes in all three cases of MD simulation. In the minor groove of the hydrated model, a spine of hydration is found as observed by x-ray crystallography and other theoretical simulations. On the basis of the rms deviations, it appears that the fully hydrated simulation has not reached a plateau at the end of the run, while the implicit simulation at constant energy seems to have converged. At constant temperature, very large oscillations in rms deviations are observed.
程序AMBER 3.0已用于生成聚（dA）·聚（dT）十聚体的分子动力学轨迹。模拟采用不同方法处理溶剂效应。将在（N，P，T）条件下包含18个抗衡离子NH4 +和4109个水分子的模拟结果与使用隐式溶剂表示的模拟运行进行比较，在隐式溶剂表示中，溶剂筛选效应通过使用 sigmoidal 距离依赖介电函数来表示。在后一种情况下，系统在微正则（N，V，E）和正则（N，V，T）条件下进行模拟。对于完全水合系统模拟，开发了一种预平衡协议，因为观察到对整个系统进行长时间渐进的加热和平衡是必要的，以避免溶质与溶剂分子之间的能量碰撞，导致溶质严重不可逆变形。报告了对DNA构象、糖环构象以及氢键（沃森-克里克氢键和三中心氢键）稳定性的详细分析。结果表明，DNA基本上保持在B构象，与标准B-DNA相比，水合模型中的DNA倾向于采用稍微扭曲、解旋和拉伸的构象。关于糖环构象，腺嘌呤残基的平均假旋转相位系统地高于胸腺嘧啶残基，除了水合模型中腺嘌呤链表现出特殊行为的情况。在这种情况下，末端碱基在C2'-内型和O4'-内型之间振荡，中间碱基则保持在C3'-内型区域。内部沃森-克里克氢键（A）HN6...O4（T）的平均寿命也取决于计算中包含的碱基对，但恒温下的隐式溶剂模拟除外。在所有三种分子动力学模拟情况下，三中心氢键的平均寿命都非常短。在水合模型的小沟中，发现了如X射线晶体学和其他理论模拟所观察到的水合脊。基于均方根偏差，似乎完全水合模拟在运行结束时尚未达到平稳状态，而恒能下的隐式模拟似乎已经收敛。在恒温下，观察到均方根偏差有非常大的振荡。
