  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.
