University of Florence, Department of Chemistry, Via Lastruccia n. 3, 50019, Sesto Fiorentino, FI, Italy.
ENEA, Portici Research Centre, DTE-ICT-HPC, P.le E. Fermi, 1, 80055, Portici, NA, Italy.
J Comput Aided Mol Des. 2021 Jan;35(1):37-47. doi: 10.1007/s10822-020-00365-3. Epub 2021 Jan 4.
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 挑战赛的背景下，我们采用非平衡（NE）化学技术，计算了两个系列主体-客体体系的标准结合自由能，其中主体为 Isaac 的 TrimerTrip、葫芦脲类似的开口空腔和 Gilson 的环糊精衍生物。采用的 NE 化学技术将增强采样分子动力学模拟与驱动快速非平衡化学轨迹相结合，通过 Jarzynski 和 Crooks NE 定理恢复自由能。GAFF2 非极化力场用于参数化。性能是可接受的，与我们在前一个 SAMPL6 主体-客体挑战中提交的 Gibbs 深腔空腔的精度相似，这证实了计算方法的可靠性，并在某些情况下暴露了 GAFF2 非极化力场的一些重要缺陷。
