Transferable force field for crystal structure predictions, investigation of performance and exploration of different rescoring strategies using DFT-D methods
Transferable force field for crystal structure predictions, investigation of performance and exploration of different rescoring strategies using DFT-D methods
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DOI：
10.1107/s2052520616006831
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发表时间：
2016-08-01
影响因子：
1.9
通讯作者：
Lill, Sten O. Nilsson
中科院分区：
文献类型：
--
作者：
Broo, Anders;Lill, Sten O. Nilsson
一种新的力场，这里被称为AZ-FF，旨在用于晶体结构预测，已经被开发出来。力场可以转移到一种新的化学类型，而不需要额外的训练或修改。这使得力场在预测新药分子的晶体结构方面非常有用，因为为每个新分子开发新力场的耗时步骤被避免了。在一组40个类似药物的分子上测试了力场的准确性，发现在观察到的晶体结构位于暂定晶体结构列表的顶部的地方，力场的准确性非常好。用离散校正密度泛函理论（DFT-D）方法重新排序进一步提高了评分。经过DFT-D几何优化后，观察到的晶体结构处于领先的前列。DFT-D方法和力场方法已经被评估用于预测诸如加热时的相变、机械性能或固有晶体溶解度等性能。讨论了在药物开发过程中与形式选择有关的风险评估中使用晶体结构预测和相关材料特性的效用。
A new force field, here called AZ-FF, aimed at being used for crystal structure predictions, has been developed. The force field is transferable to a new type of chemistry without additional training or modifications. This makes the force field very useful in the prediction of crystal structures of new drug molecules since the time-consuming step of developing a new force field for each new molecule is circumvented. The accuracy of the force field was tested on a set of 40 drug-like molecules and found to be very good where observed crystal structures are found at the top of the ranked list of tentative crystal structures. Re-ranking with dispersion-corrected density functional theory (DFT-D) methods further improves the scoring. After DFT-D geometry optimization the observed crystal structure is found at the leading top of the ranking list. DFT-D methods and force field methods have been evaluated for use in predicting properties such as phase transitions upon heating, mechanical properties or intrinsic crystalline solubility. The utility of using crystal structure predictions and the associated material properties in risk assessment in connection with form selection in the drug development process is discussed.