Implementation of the QUBE Force Field in SOMD for High-Throughput Alchemical Free-Energy Calculations.
Lauren NelsonSofia BariamiChris RingroseJoshua T HortonVadiraj KurdekarAntonia S J S MeyJulien MichelDaniel J ColePublished in: Journal of chemical information and modeling (2021)
The quantum mechanical bespoke (QUBE) force-field approach has been developed to facilitate the automated derivation of potential energy function parameters for modeling protein-ligand binding. To date, the approach has been validated in the context of Monte Carlo simulations of protein-ligand complexes. We describe here the implementation of the QUBE force field in the alchemical free-energy calculation molecular dynamics simulation package SOMD. The implementation is validated by demonstrating the reproducibility of absolute hydration free energies computed with the QUBE force field across the SOMD and GROMACS software packages. We further demonstrate, by way of a case study involving two series of non-nucleoside inhibitors of HIV-1 reverse transcriptase, that the availability of QUBE in a modern simulation package that makes efficient use of graphics processing unit acceleration will facilitate high-throughput alchemical free-energy calculations.
Keyphrases
- monte carlo
- high throughput
- molecular dynamics simulations
- single molecule
- primary care
- molecular dynamics
- healthcare
- density functional theory
- quality improvement
- molecular docking
- single cell
- hepatitis c virus
- protein protein
- antiretroviral therapy
- human immunodeficiency virus
- hiv positive
- amino acid
- binding protein
- risk assessment
- small molecule
- magnetic resonance
- diffusion weighted imaging
- computed tomography
- climate change
- energy transfer