跨越化学空间的数据驱动粗粒度模型的分辨率极限
Resolution limit of data-driven coarse-grained models spanning chemical space
摘要：
提高材料设计和发现的效率仍然是一个重大挑战，特别是考虑到化合物空间的尺寸过大。使用化学可转移的粗粒度模型使不同的分子片段能够映射到相同的珠类型，同时还降低了计算费用。这些特性进一步提高了筛选效率，因为许多化合物通过使用单一粗粒度模拟进行筛选，有效地减小了化合物空间的大小。在这里，我们提出了新的标准，合理设计的粗粒度模型，允许优化其化学可转移性和评估的马提尼模型在这个框架内。我们进一步调查的范围内，这种化学可转移性参数化三个马丁尼样模型，其中珠类型的数量范围从5到16个不同的力场。然后，我们实施贝叶斯方法来确定哪些化学基团更可能存在于对应于每个模型的特定珠类型的片段上。我们证明，可以通过使用具有较少珠类型的力场来获得与Martini相当的性能和精度水平。然而，包括更多微珠类型的优点是减少了关于将这些微珠类型反向映射到特定化学物质的不确定性。正如减小粗颗粒的尺寸会导致构象空间的更精细映射，增加珠类型的数量会产生化合物空间的更精细映射。最后，我们注意到，由于映射到单个马提尼珠的化学片段的尺寸相对较大，当使用水/辛醇分配自由能作为粗粒化化合物空间时的唯一描述符时，出现了明显的分辨率限制。
英文摘要：
Increasing the efficiency of materials design and discovery remains a significant challenge, especially given the prohibitively large size of chemical compound space. The use of a chemically transferable coarse-grained model enables different molecular fragments to map to the same bead type, while also reducing computational expense. These properties further increase screening efficiency, as many compounds are screened through the use of a single coarse-grained simulation, effectively reducing the size of chemical compound space. Here, we propose new criteria for the rational design of coarse-grained models that allows for the optimization of their chemical transferability and evaluate the Martini model within this framework. We further investigate the scope of this chemical transferability by parameterizing three Martini-like models, in which the number of bead types ranges from five to sixteen for the different force fields. We then implement a Bayesian approach to determining which chemical groups are more likely to be present on fragments corresponding to specific bead types for each model. We demonstrate that a level of performance and accuracy comparable to Martini can be obtained by using a force field with fewer bead types. However, the advantage of including more bead types is a reduction of uncertainty with respect to back-mapping these bead types to specific chemistries. Just as reducing the size of the coarse-grained particles leads to a finer mapping of conformational space, increasing the number of bead types yields a finer mapping of chemical compound space. Finally, we note that, due to the relatively large size of the chemical fragments that map to a single martini bead, a clear resolution limit arises when using the water/octanol partition free energy as the only descriptor when coarse-graining chemical compound space.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
