Garcia A E, Soumpasis D M, Jovin T M
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, New Mexico 87545.
Biophys J. 1994 Jun;66(6):1742-55. doi: 10.1016/S0006-3495(94)80970-1.
The dynamics and stability of four DNA duplexes are studied by means of molecular dynamics simulations. The four molecules studied are combinations of 4, 15 bases long, single-stranded oligomers, F1, F2, F3, and F4. The sequence of these single strand oligomers are chosen such that F1-F2 and F3-F4 form parallel (ps) DNA double helices, whereas F1-F4 and F2-F3 form antiparallel-stranded (aps) DNA double helices. Simulations were done at low (100 K) and room (300 K) temperatures. At low temperatures the dynamics are quasi-harmonic and the analysis of the trajectories gives good estimates of the low frequency vibrational modes and density of states. These are used to estimate the linear (harmonic) contribution of local fluctuations to the configurational entropy of the systems. Estimates of the differences in enthalpy between ps and aps duplexes show that aps double helices are more stable than the corresponding ps duplexes, in agreement with experiments. At higher temperatures, the distribution of the fluctuations around the average structures are multimodal and estimates of the configurational entropy cannot be obtained. The multi-basin, nonlinear character of the dynamics at 300 K is established using a novel method which extracts large amplitude nonlinear motions from the molecular dynamics trajectories. Our analysis shows that both ps DNA exhibit much larger fluctuations than the two aps DNA. The large fluctuations of ps DNA are explained in terms of correlated transitions in the beta, epsilon, and zeta backbone dihedral angles.
通过分子动力学模拟研究了四种DNA双链体的动力学和稳定性。所研究的四个分子是由长度为4个和15个碱基的单链寡聚物F1、F2、F3和F4组合而成。选择这些单链寡聚物的序列，使得F1 - F2和F3 - F4形成平行（ps）DNA双螺旋，而F1 - F4和F2 - F3形成反平行链（aps）DNA双螺旋。模拟在低温（100 K）和室温（300 K）下进行。在低温下，动力学为准谐波，对轨迹的分析给出了低频振动模式和态密度的良好估计。这些用于估计局部涨落对系统构型熵的线性（谐波）贡献。ps和aps双链体之间焓差的估计表明，aps双螺旋比相应的ps双链体更稳定，这与实验结果一致。在较高温度下，围绕平均结构的涨落分布是多峰的，无法获得构型熵的估计值。使用一种从分子动力学轨迹中提取大振幅非线性运动的新方法，确定了300 K时动力学的多盆地、非线性特征。我们的分析表明，两种ps DNA的涨落都比两种aps DNA大得多。ps DNA的大涨落是根据β、ε和ζ主链二面角的相关转变来解释的。
