Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Mol Model. 2009 Nov;15(11):1383-9. doi: 10.1007/s00894-009-0504-3. Epub 2009 May 6.
As computational resources increase, molecular dynamics simulations of biomolecules are becoming an increasingly informative complement to experimental studies. In particular, it has now become feasible to use multiple initial molecular configurations to generate an ensemble of replicate production-run simulations that allows for more complete characterization of rare events such as ligand-receptor unbinding. However, there are currently no explicit guidelines for selecting an ensemble of initial configurations for replicate simulations. Here, we use clustering analysis and steered molecular dynamics simulations to demonstrate that the configurational changes accessible in molecular dynamics simulations of biomolecules do not necessarily correlate with observed rare-event properties. This informs selection of a representative set of initial configurations. We also employ statistical analysis to identify the minimum number of replicate simulations required to sufficiently sample a given biomolecular property distribution. Together, these results suggest a general procedure for generating an ensemble of replicate simulations that will maximize accurate characterization of rare-event property distributions in biomolecules.
随着计算资源的增加，生物分子的分子动力学模拟正在成为实验研究的一个越来越有价值的补充。特别是，现在已经可以使用多个初始分子构象来生成一组复制的生产运行模拟，从而更完整地描述配体-受体解联等罕见事件。然而，目前还没有明确的指南来选择用于复制模拟的初始构象集合。在这里，我们使用聚类分析和导向分子动力学模拟来证明，生物分子分子动力学模拟中可及的构象变化不一定与观察到的罕见事件性质相关。这为选择一组具有代表性的初始构象提供了信息。我们还使用统计分析来确定复制模拟所需的最少数量，以充分采样给定的生物分子性质分布。总之，这些结果为生成一组复制模拟提供了一种通用方法，该方法将最大限度地提高对生物分子罕见事件性质分布进行准确描述的能力。
