Blind Predictions for the SAMPL9 Host-Guest Challenge

We present our blind predictions for the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL), 9th 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, M Pagliai, M Karrenbrock, G Guarnieri, F Iannone, Procacci, J Chem Theory Comput, 16, 7260, 2020]. Experimental binding free energies for the thirteen host-guest complexes will be disclosed by November 2021.