Are current molecular dynamics force fields too helical?
Are current molecular dynamics force fields too helical?
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DOI：
10.1529/biophysj.108.132696
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发表时间：
2008-07-01
影响因子：
3.4
通讯作者：
Hummer, Gerhard
中科院分区：
文献类型：
--
作者：
Best, Robert B.;Buchete, Nicolae-Viorel;Hummer, Gerhard
精确的力场是分子动力学模拟成功的关键。与大多数力场的构象偏好明显相反，最近的NMR实验表明，短聚丙氨酸肽在水中几乎完全占据聚脯氨酸II结构。为了研究这个明显的矛盾，及其分支。为了评估分子力场和未折叠蛋白质的结构，我们使用12种不同的力场和3种不同的肽末端基团对Ala（5）在水中进行了广泛的模拟（总时间类似于5 μ s）。使用经验或密度泛函为基础的Karplus关系的J-耦合，我们发现，大多数电流力场过度填充的α-区域，定量结果取决于Karplus关系的选择和肽末端。即使在重新加权以匹配实验之后，我们发现Ala（5）保留了显著的α和β群体。事实上，有几个力场在重新加权之前与实验数据很好地匹配，并且具有显著的螺旋布居。我们的结论是，根本的变化，最好的电流力场是没有必要的，根据NMR数据。然而，短肽的实验为系统地改进当前的模拟模型开辟了道路。
Accurate force fields are essential for the success of molecular dynamics simulations. In apparent contrast to the conformational preferences of most force fields, recent NMR experiments suggest that short polyalanine peptides in water populate the polyproline II structure almost exclusively. To investigate this apparent contradiction, with its rami. cations for the assessment of molecular force fields and the structure of unfolded proteins, we performed extensive simulations of Ala(5) in water (similar to 5 mu s total time), using twelve different force fields and three different peptide terminal groups. Using either empirical or density-functional-based Karplus relations for the J-couplings, we find that most current force fields do overpopulate the alpha-region, with quantitative results depending on the choice of Karplus relation and on the peptide termini. Even after reweighting to match experiment, we find that Ala(5) retains significant alpha- and beta-populations. In fact, several force fields match the experimental data well before reweighting and have a significant helical population. We conclude that radical changes to the best current force fields are not necessary, based on the NMR data. Nevertheless, experiments on short peptides open the way toward the systematic improvement of current simulation models.