CAREER: Understanding the thermodynamics of crystalline materials using advanced molecular simulation sampling methods

固相材料理论在很大程度上集中在零温度晶体极小值及其附近的调和近似上。在现实系统中，如药物晶体或用于功能材料的金属氧化物，常温或高温性能是最受关注的。这意味着重要的量是自由能极小值和热力学系综，而不是势能极小值和固定结构。此前很少有研究考察比Lennard-Jones球体或原子盐更复杂的固体的自由能图景。这一建议将以新的方式模拟多个热力学系综的方法结合在一起，以实现现实晶体系统所需的必要采样水平。所提出的方法将以一种直接的方式扩展到多组分晶体和潜在的提高精度的函数。更好地了解分子晶体的热力学和提高定量预测其性质的能力对于继续改进药物开发管道至关重要，使药物能够更安全、更容易和更廉价地配制和加工。这里开发的方法还将用于各种结晶材料的预测工具，包括颜料、农药和其他农用化学品、食品添加剂、电子材料、陶瓷和炸药。

1351635ShirtsThe theory of solid phase materials has focused to a large extent on zero temperature crystal minima and harmonic approximations around these minima. In realistic systems, such as crystals of pharmaceutical agents or metal oxides for functional materials, the room temperature or high temperature properties are of most interest. This means free energy minima and thermodynamic ensembles are the important quantities, rather than potential energy minima and fixed structures. Little previous research has examined the free energy landscape of solids more complex than Lennard-Jones spheres or atomic salts. This proposal brings together methods for simulating multiple thermodynamic ensembles in new ways in order to achieve the necessary levels of sampling required for realistic crystal systems. The proposed methods will scale in a straightforward way to multicomponent crystals and to potential functions of increasing accuracy.A better understanding of the thermodynamics of molecular crystals and an improved ability to quantitatively predict their properties is vital for continued improvement of the pharmaceutical development pipeline, allowing drugs to be formulated and processed more safely, easily and cheaply. The methods developed here will also be useful for predictive tools for processing of a broad range of crystalline materials including pigments, pesticides and other agrochemicals, food additives, electronic materials, ceramics and explosives.