J Chem Phys. 2022 Apr 28;156(16):164104. doi: 10.1063/5.0086640.
ABSTRACT
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.
PMID:35490003 | DOI:10.1063/5.0086640
