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.

SAMPL7 blind predictions using nonequilibrium alchemical approaches

Guarnieri, Guido
2021-01-01

Abstract

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.
2021
Binding free energy
Crooks theorem
Fast switching
HREX
Hamiltonian Replica Exchange
Non-equilibrium
SAMPL7
Solute Tempering
Torsional tempering
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12079/66248
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