Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenges provide routes to compare chemical quantities determined using computational chemistry approaches to experimental measurements that are shared after the competition. For this effort, several computational methods have been used to calculate the binding energies of Octa Acid (OA) and exo-Octa Acid (exoOA) host–guest systems for SAMPL7. The initial poses for molecular dynamics (MD) were generated by molecular docking. Binding free energy calculations were performed using molecular mechanics combined with Poisson–Boltzmann or generalized Born surface area solvation (MMPBSA/MMGBSA) approaches. The factors that affect the utility of the MMPBSA/MMGBSA approaches including solvation, partial charge, and solute entropy models were also analyzed. In addition to MD calculations, quantum mechanics (QM) calculations were performed using several different density functional theory (DFT) approaches. From SAMPL6 results, B3PW91-D3 was found to overestimate binding energies though it was effective for geometry optimizations, so it was considered for the DFT geometry optimizations in the current study, with single-point energy calculations carried out with B2PLYP-D3 with double-, triple-, and quadruple-ζ level basis sets. Accounting for dispersion effects, and solvation models was deemed essential for the predictions. MMGBSA and MMPBSA correlated better to experiment when used in conjunction with an empirical/linear correction.

蛋白质和配体建模的统计评估 (SAMPL) 挑战提供了将使用计算化学方法确定的化学量与竞赛后共享的实验测量值进行比较的途径。为此，已经使用了几种计算方法来计算 SAMPL7 的八酸 (OA) 和外八酸 (exo-Octa) 主客体系统的结合能。分子动力学 (MD) 的初始姿态是通过分子对接生成的。结合自由能计算使用分子力学结合泊松-玻尔兹曼或广义玻恩表面积溶剂化 (MMPBSA/MMGBSA) 方法进行。还分析了影响 MMPBSA/MMGBSA 方法效用的因素，包括溶剂化、部分电荷和溶质熵模型。除了MD计算，使用几种不同的密度泛函理论 (DFT) 方法进行量子力学 (QM) 计算。从 SAMPL6 结果，发现 B3PW91-D3 虽然对几何优化有效，但被发现高估了结合能，因此在当前研究中考虑将其用于 DFT 几何优化，使用 B2PLYP-D3 进行单点能量计算、三重和四重 ζ 级基组。考虑到分散效应和溶剂化模型被认为对预测至关重要。当与经验/线性校正结合使用时，MMGBSA 和 MMPBSA 与实验的相关性更好。尽管 B3PW91-D3 对几何优化有效，但被发现高估了结合能，因此在当前研究中考虑将其用于 DFT 几何优化，使用 B2PLYP-D3 进行单点能量计算，具有双、三、和四 ζ 级基组。考虑到分散效应和溶剂化模型被认为对预测至关重要。当与经验/线性校正结合使用时，MMGBSA 和 MMPBSA 与实验的相关性更好。尽管 B3PW91-D3 对几何优化有效，但被发现高估了结合能，因此在当前研究中考虑将其用于 DFT 几何优化，使用 B2PLYP-D3 进行单点能量计算，具有双、三、和四 ζ 级基组。考虑到分散效应和溶剂化模型被认为对预测至关重要。当与经验/线性校正结合使用时，MMGBSA 和 MMPBSA 与实验的相关性更好。