论文标题
Sampl9使用非平衡炼金术方法进行盲目预测
SAMPL9 blind predictions using nonequilibrium alchemical approaches
论文作者
论文摘要
我们介绍了对蛋白质和配体（Sampl）的统计评估的盲目预测，第9次挑战，重点是WP6（羧基 - 柱[6] Arene）与铵/二硫代阳离子来宾的结合。已经使用最近开发的虚拟双系统单盒方法计算了宿主 - 圈结合自由能，该方法是基于绑定和未绑定的终端的增强采样，然后快速切换非平衡的炼金术模拟[M MacChiagodena [M MacChiagodena，M Pagliai Iannone，Procacci，J化学理论计算，16，7260，2020]。就Pearson和Kendall系数而言，表演是可以接受的，并且通常比我们提交的calixarenes，类似黄瓜的开放式Cavitand和beta-cyclodextrines在先前的Sampl Host-GueST挑战中提出的要好，从而确认了无量准性方法的可靠性，以确认实现绝对粘合能量的无量化可依据。与以前的提交相比，我们发现，我们归因于通过假设中和背景等离子体来解决有限电荷校正的方式。
We present our blind predictions for the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL), 9th challenge, focusing on 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, M Pagliai, M Karrenbrock, G Guarnieri, F Iannone, Procacci, J Chem Theory Comput, 16, 7260, 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, nonetheless, 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.
