ci0c00648_si_001.pdf (347.88 kB)
grand: A Python Module for Grand Canonical Water Sampling in OpenMM
journal contribution
posted on 2020-09-19, 17:29 authored by Marley
L. Samways, Hannah E. Bruce Macdonald, Jonathan W. EssexNetworks
of water molecules can play a critical role at the protein–ligand
interface and can directly influence drug–target interactions.
Grand canonical methods aid in the sampling of these water molecules,
where conventional molecular dynamics equilibration times are often
long, by allowing waters to be inserted and deleted from the system,
according to the chemical potential. Here, we present our open source
Python module, grand (https://github.com/essex-lab/grand), which allows molecular dynamics simulations to be performed in
conjunction with grand canonical Monte Carlo sampling, using the OpenMM
simulation engine. We demonstrate the accuracy of this module by reproducing
the density of bulk water observed from constant pressure simulations.
Application of this code to the bovine pancreatic trypsin inhibitor
protein reproduces three buried crystallographic water sites that
are poorly sampled using conventional molecular dynamics.