Resolution limit of data-driven coarse-grained models spanning chemical space.
Resolution limit of data-driven coarse-grained models spanning chemical space.
复制标题
DOI：
10.1063/1.5119101
复制
发表时间：
2019-07
期刊：
影响因子：
--
通讯作者：
K. Kanekal;T. Bereau
中科院分区：
文献类型：
--
作者：
K. Kanekal;T. Bereau
考虑到化合物空间(CCS)的巨大规模，提高材料设计的效率仍然是一个巨大的挑战。化学可转移粗粒模型的使用使不同的分子片段能够映射到相同的珠子类型，显著提高了筛选效率。在这里，我们为粗粒度模型的设计提出了新的标准，允许优化其化学可转移性，并在此框架内评估Martini模型。我们通过对三个珠子类型从5个到16个的类Martini模型的参数化，进一步研究了这种可传递的范围。这些力场与现有的Martini环境完全兼容，因为它们是通过内插Martini相互作用矩阵来参数化的。然后，我们实施贝叶斯方法来确定与每个模型的特定珠子类型对应的碎片上可能存在哪些化学基团。我们证明，使用水/辛醇分配自由能(ΔGW→Ol)作为衡量标准进行比较，可以在具有较少珠子类型的力场中获得与马提尼相当的精度水平。然而，包含更多珠子类型的好处是减少了将这些珠子类型反向映射到特定化学物质时的不确定性。正如减小粗粒度颗粒的大小会导致构象空间的更精细映射一样，增加珠子类型的数量会产生CCS的更精细映射。最后，我们注意到，由于映射到单个马提尼珠子的碎片尺寸很大，在粗粒化CCS时使用ΔGW→Ol作为唯一描述符时会出现分辨率限制。
Increasing the efficiency of materials design remains a significant challenge given the large size of chemical compound space (CCS). The use of a chemically transferable coarse-grained model enables different molecular fragments to map to the same bead type, significantly increasing screening efficiency. Here, we propose new criteria for the design of coarse-grained models allowing for the optimization of their chemical transferability and evaluate the Martini model within this framework. We further investigate the scope of this transferability by parameterizing three Martini-like models in which the number of bead types ranges from 5 to 16. These force fields are fully compatible with existing Martini environments because they are parameterized by interpolating the Martini interaction matrix. We then implement a Bayesian approach to determining which chemical groups are likely to be present on fragments corresponding to specific bead types for each model. We demonstrate that a level of accuracy comparable to Martini is obtained with a force field with fewer bead types, using the water/octanol partitioning free energy (ΔGW→Ol) as our metric for comparison. However, the advantage of including more bead types is a reduction of uncertainty when 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 CCS. Finally, we note that, due to the large size of fragments mapping to a single Martini bead, a resolution limit arises when using ΔGW→Ol as the only descriptor when coarse-graining CCS.