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

preprint
submitted on 20.10.2020, 09:25 and posted on 20.10.2020, 11:04 by Lauren Nelson, Sofia Bariami, Chris Ringrose, Joshua Horton, Vadiraj Kurdekar, Antonia Mey, Julien Michel, Daniel Cole

The quantum mechanical bespoke (QUBE) force field approach has been developed to facilitate the automated derivation of potential energy function parameters for modelling 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 computing relative binding free energies for two congeneric series of non-nucleoside inhibitors of HIV-1 reverse transcriptase using QUBE and AMBER/GAFF force fields. The availability of QUBE in a modern simulation package that makes efficient use of GPU acceleration will greatly facilitate future high-throughput alchemical free energy calculation studies.

Funding

Peta-5: A National Facility for Petascale Data Intensive Computation and Analytics

Engineering and Physical Sciences Research Council

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Application of large-scale quantum mechanical simulation to the development of future drug therapies

Engineering and Physical Sciences Research Council

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History

Email Address of Submitting Author

daniel.cole@ncl.ac.uk

Institution

Newcastle University

Country

United Kingdom

ORCID For Submitting Author

0000-0003-2933-0719

Declaration of Conflict of Interest

No conflict of interest

Licence

Exports