Implementation of the QUBE Force Field in SOMD for High-Throughput Alchemical Free-Energy Calculations

Lauren Nelson, Sofia Bariami, Chris Ringrose, Joshua T. Horton, Vadiraj Kurdekar, Antonia S. J. S. Mey, Julien Michel, Daniel J. Cole

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)2124–2130
JournalJournal of Chemical Information and Modeling
Issue number5
Early online date22 Apr 2021
Publication statusPublished - 24 May 2021


Dive into the research topics of 'Implementation of the QUBE Force Field in SOMD for High-Throughput Alchemical Free-Energy Calculations'. Together they form a unique fingerprint.

Cite this