Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
J Phys Chem B. 2010 Jan 14;114(1):429-36. doi: 10.1021/jp9052665.
Two force fields, the GROMOS53A5/53A6 (united atom) and the AMBER95 (all atom) parameter sets, coupled with partial atomic charges derived from quantum mechanical calculations were evaluated for their ability to reproduce the known crystalline forms of the polyols mannitol and sorbitol. The force fields were evaluated using molecular dynamics simulations at 10 K (which is akin to potential energy minimization) with the simulation cell lengths and angles free to evolve. Both force fields performed relatively poorly, not being able to simultaneously reproduce all of the crystal structures within a 5% deviation level. The parameter sets were then systematically optimized using sensitivity analysis, and a revised AMBER95 set was found to reproduce the crystal structures with less than 5% deviation from experiment. The stability of the various crystalline forms for each of the parameter sets (original and revised) was then assessed in extended MD simulations at 298 K and 1 bar covering 1 ns simulation time. The AMBER95 parameter sets (original and revised) were found to be effective in reproducing the crystal structures in these more stringent tests. Remarkably, the performance of the original AMBER95 parameter set was found to be slightly better than that of the revised set in these simulations at 298 K. The results of this study suggest that, whenever feasible, one should include molecular simulations at elevated temperatures when optimizing parameters.
两种力场，GROMOS53A5/53A6（统一原子）和 AMBER95（全原子）参数集，以及从量子力学计算中得出的部分原子电荷，用于评估它们复制多元醇甘露醇和山梨糖醇已知晶体形式的能力。使用分子动力学模拟在 10 K 下（类似于势能最小化）评估力场，模拟单元的长度和角度可以自由演变。两种力场的性能都相对较差，无法同时在 5%的偏差水平内复制所有晶体结构。然后使用敏感性分析对参数集进行系统优化，并发现经过修正的 AMBER95 集可以在低于 5%的实验偏差内复制晶体结构。然后在 298 K 和 1 巴的条件下进行扩展 MD 模拟，模拟时间为 1 ns，评估每个参数集（原始和修正）的各种晶体形式的稳定性。发现 AMBER95 参数集（原始和修正）在这些更严格的测试中能够有效地复制晶体结构。值得注意的是，在这些 298 K 的模拟中，原始 AMBER95 参数集的性能略优于修正集。这项研究的结果表明，只要可行，在优化参数时，应在升高的温度下进行分子模拟。
