Many physical properties of small organic molecules are dependent on the current crystal packing, or polymorph, of the material, including bioavailability of pharmaceuticals, optical properties of dyes, and charge transport properties of semiconductors. Predicting the most stable crystalline form at a given temperature and pressure requires determining the crystalline form with the lowest relative Gibbs free energy. Effective computational prediction of the most stable polymorph could save significant time and effort in the design of novel molecular crystalline solids or predict their behavior under new conditions. In this study, we introduce a new approach using multistate reweighting to address the problem of determining solid-solid phase diagrams and apply this approach to the phase diagram of solid benzene. For this approach, we perform sampling at a selection of temperature and pressure states in the region of interest. We use multistate reweighting methods to determine the reduced free energy differences between T and P states within a given polymorph and validate this phase diagram using several measures. The relative stability of the polymorphs at the sampled states can be successively interpolated from these points to create the phase diagram by combining these reduced free energy differences with a reference Gibbs free energy difference between polymorphs. The method also allows for straightforward estimation of uncertainties in the phase boundary. We also find that when properly implemented, multistate reweighting for phase diagram determination scales better with the size of the system than previously estimated.

中文翻译：

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使用重加权和自由能表面插值预测固-固相图

有机小分子的许多物理性质取决于材料的当前晶体堆积或多晶型物，包括药物的生物利用度，染料的光学性质和半导体的电荷传输性质。在给定的温度和压力下预测最稳定的晶型需要确定相对吉布斯自由能最低的晶型。对最稳定的多晶型物进行有效的计算预测可以节省设计新型分子结晶固体或在新条件下的行为时可节省大量的时间和精力。在这项研究中，我们介绍了一种使用多态重加权的新方法来解决确定固-固相图的问题，并将该方法应用于固体苯的相图。对于这种方法，我们在感兴趣区域的选定温度和压力状态下执行采样。我们使用多状态重新加权方法来确定减少的自由能之间的差异给定多晶型物内的T和P状态，并使用几种方法来验证该相图。通过将这些减少的自由能差与多态之间的参考吉布斯自由能差结合起来，可以从这些点上连续插入多态型在采样状态下的相对稳定性，以创建相图。该方法还允许直接估计相位边界中的不确定性。我们还发现，如果正确实施，则用于相图确定的多状态重加权会比以前估计的系统规模更好。