Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy.
ENEA, Portici Research Centre, DTE-ICT-HPC, P.le E. Fermi, 1, I-80055 Portici, NA, Italy.
J Chem Phys. 2022 Apr 28;156(16):164104. doi: 10.1063/5.0086640.
We present our blind predictions for the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL), ninth challenge, focusing on the binding of WP6 (carboxy-pillar[6]arene) with ammonium/diammonium cationic guests. Host-guest binding free energies have been calculated using the recently developed virtual double system single box approach, based on the enhanced sampling of the bound and unbound end-states followed by fast switching nonequilibrium alchemical simulations [M. Macchiagodena et al., J. Chem. Theory Comput. 16, 7160 (2020)]. As far as Pearson and Kendall coefficients are concerned, performances were acceptable and, in general, better than those we submitted for calixarenes, cucurbituril-like open cavitand, and beta-cyclodextrines in previous SAMPL host-guest challenges, confirming the reliability of nonequilibrium approaches for absolute binding free energy calculations. In comparison with previous submissions, we found a rather large mean signed error that we attribute to the way the finite charge correction was addressed through the assumption of a neutralizing background plasma.
我们对蛋白质和配体建模的统计评估（SAMPL）第九次挑战进行了盲测，重点是 WP6（羧基-柱[6]芳烃）与铵/二铵阳离子客体的结合。使用最近开发的虚拟双体系单盒方法，基于结合和未结合末端状态的增强采样，以及快速切换非平衡的非平衡模拟，计算了主客体结合自由能[M. Macchiagodena 等人，J. Chem. Theory Comput. 16, 7160（2020）]。就 Pearson 和 Kendall 系数而言，性能是可以接受的，通常比我们在前几次 SAMPL 主客体挑战中提交的杯芳烃、葫芦脲类开腔囊和β-环糊精要好，这证实了非平衡方法对于绝对结合自由能计算的可靠性。与以前的提交相比，我们发现了一个相当大的平均有符号误差，我们将其归因于通过假设中性背景等离子体来解决有限电荷校正的方式。
