In the context of the SAMPL7 challenge, we computed, employing a non-equilibrium (NE) alchemical technique, the standard binding free energy of two series of host-guest systems, involving as a host the Isaac’s TrimerTrip, a Cucurbituril-like open cavitand, and the Gilson’s Cyclodextrin derivatives. The adopted NE alchemy combines enhanced sampling molecular dynamics simulations with driven fast out-of-equilibrium alchemical trajectories to recover the free energy via the Jarzynski and Crooks NE theorems. The GAFF2 non-polarizable force field was used for the parametrization. Performances were acceptable and similar in accuracy to those we submitted for Gibb’s Deep Cavity Cavitands in the previous SAMPL6 host-guest challenge, confirming the reliability of the computational approach and exposing, in some cases, some important deficiencies of the GAFF2 non-polarizable force field.

在 SAMPL7 挑战的背景下，我们使用非平衡 (NE) 炼金术技术计算了两个系列主客体系统的标准结合自由能，其中包括作为宿主的 Isaac 的 TrimerTrip，一种类似葫芦脲的开放腔和吉尔森环糊精衍生物。采用的 NE 炼金术将增强的采样分子动力学模拟与驱动的快速失衡炼金术轨迹相结合，通过 Jarzynski 和 Crooks NE 定理恢复自由能。GAFF2 不可极化力场用于参数化。性能是可以接受的，并且与我们在之前的 SAMPL6 主客挑战中为 Gibb 的深腔空洞提交的性能相似，证实了计算方法的可靠性，并在某些情况下暴露了，