论文标题
分子晶体中构象多态性的集体变量
Collective Variables for Conformational Polymorphism in Molecular Crystals
论文作者
论文摘要
在药物,染料和农药产业中,控制分子晶体中的多态性至关重要。但是,由于相关的长时间标准($> 1 \,μs$),其理论描述极具挑战性。我们提出了一个有效的程序,用于识别促进分子动力学模拟中构象多晶型物之间过渡的集体变量。它涉及将简单的维度降低算法应用于与与每个polymorph相对应的隔离构象异构体的简短($ \ sim PS $)模拟的数据。在重要的能量材料Cl-20的挑战性情况下,我们证明了我们方法的实用性,该材料在环境压力下具有三个无水构象的多晶型物。在元动力学模拟中使用这些集体变量,我们观察到偏置轨迹中所有固体多晶型物之间的过渡。我们重建自由能表面,并在从一个已知的多晶型物到另一种多晶型物的过渡中识别以前未知的缺陷和中间形式。我们的方法提供了对柔性分子晶体的复杂构象多态性跃迁的见解。
Controlling polymorphism in molecular crystals is crucial in the pharmaceutical, dye, and pesticide industries. However, its theoretical description is extremely challenging, due to the associated long timescales ($ > 1 \, μs$). We present an efficient procedure for identifying collective variables that promote transitions between conformational polymorphs in molecular dynamics simulations. It involves applying a simple dimensionality reduction algorithm to data from short ($\sim ps$) simulations of the isolated conformers that correspond to each polymorph. We demonstrate the utility of our method in the challenging case of the important energetic material, CL-20, which has three anhydrous conformational polymorphs at ambient pressure. Using these collective variables in Metadynamics simulations, we observe transitions between all solid polymorphs in the biased trajectories. We reconstruct the free energy surface and identify previously unknown defect and intermediate forms in the transition from one known polymorph to another. Our method provides insights into complex conformational polymorphic transitions of flexible molecular crystals.