Obtaining QM/MM binding free energies in the SAMPL8 drugs of abuse challenge: indirect approaches.
Obtaining QM/MM binding free energies in the SAMPL8 drugs of abuse challenge: indirect approaches.
复制标题
DOI：
10.1007/s10822-022-00443-8
复制
发表时间：
2022-04
影响因子：
3.5
通讯作者：
中科院分区：
文献类型：
--
作者：
准确预测自由能差对于实现合理药物设计的全部潜力至关重要。不幸的是，高水平的准确性往往需要计算昂贵的QM/MM哈密顿。幸运的是，在严格的自由能模拟中采用QM/MM方法的成本可以通过使用所谓的“间接”方法来降低QM/MM自由能，其中通过在感兴趣的经典端点处的QM/MM“校正”来避免对QM/MM模拟的需要。在这里，我们专注于计算QM/MM结合自由能的背景下，SAMPL 8滥用药物的主客体挑战。在5个QM/MM校正与力匹配提交中，PM 6-D3 H4/MM排名提交证明了最佳的整体QM/MM条目，实验结果的RMSE为2.43 kcal/mol（排名提交中最佳），Pearson相关性为0.78（排名提交中第二佳），Kendall相关性为0.52（排名提交中最佳）。在线版本包含补充材料，可通过10.1007/s10822-022-00443-8获取。
Accurately predicting free energy differences is essential in realizing the full potential of rational drug design. Unfortunately, high levels of accuracy often require computationally expensive QM/MM Hamiltonians. Fortuitously, the cost of employing QM/MM approaches in rigorous free energy simulation can be reduced through the use of the so-called “indirect” approach to QM/MM free energies, in which the need for QM/MM simulations is avoided via a QM/MM “correction” at the classical endpoints of interest. Herein, we focus on the computation of QM/MM binding free energies in the context of the SAMPL8 Drugs of Abuse host–guest challenge. Of the 5 QM/MM correction coupled with force-matching submissions, PM6-D3H4/MM ranked submission proved the best overall QM/MM entry, with an RMSE from experimental results of 2.43 kcal/mol (best in ranked submissions), a Pearson’s correlation of 0.78 (second-best in ranked submissions), and a Kendall correlation of 0.52 (best in ranked submissions). The online version contains supplementary material available at 10.1007/s10822-022-00443-8.
影响因子：
3.5
作者：
Krämer A;Hudson PS;Jones MR;Brooks BR
通讯作者：
Brooks BR