SAMPL7 blind predictions using nonequilibrium alchemical approaches

• Published in: Journal of computer-aided molecular design Vol. 35; no. 1; pp. 37 - 47
• Main Authors: Procacci, Piero, Guarnieri, Guido
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 2021; Springer Nature B.V
• Subjects: Animal Anatomy; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Cyclodextrins; Free energy; Histology; Molecular dynamics; Morphology; Parameterization; Physical Chemistry; Supramolecular compounds; SAMPL7; Hamiltonian Replica Exchange; Solute Tempering; Binding free energy; Crooks theorem; HREX; Non-equilibrium; Fast switching; Torsional tempering
• ISSN: 0920-654X; 1573-4951
• DOI: 10.1007/s10822-020-00365-3

In the context of the SAMPL7 challenge, we computed, employing a non-equilibrium (NE) alchemical technique, the standard binding free energy of two series of host-guest systems, involving as a host the Isaac’s TrimerTrip, a Cucurbituril-like open cavitand, and the Gilson’s Cyclodextrin derivatives. The adopted NE alchemy combines enhanced sampling molecular dynamics simulations with driven fast out-of-equilibrium alchemical trajectories to recover the free energy via the Jarzynski and Crooks NE theorems. The GAFF2 non-polarizable force field was used for the parametrization. Performances were acceptable and similar in accuracy to those we submitted for Gibb’s Deep Cavity Cavitands in the previous SAMPL6 host-guest challenge, confirming the reliability of the computational approach and exposing, in some cases, some important deficiencies of the GAFF2 non-polarizable force field.