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QUBEKit: Automating the Derivation of Force Field Parameters from Quantum Mechanics

preprint
revised on 11.02.2019 and posted on 11.02.2019 by Joshua Horton, Alice Allen, Leela Dodda, Daniel Cole

Modern molecular mechanics force fields are widely used for modelling the dynamics and interactions of small organic molecules using libraries of transferable force field parameters. For molecules outside the training set, parameters may be missing or inaccurate, and in these cases, it may be preferable to derive molecule-specific parameters. Here we present an intuitive parameter derivation toolkit, QUBEKit (QUantum mechanical BEspoke Kit), which enables the automated generation of system-specific small molecule force field parameters directly from quantum mechanics. QUBEKit is written in python and combines the latest QM parameter derivation methodologies with a novel method for deriving the positions and charges of off-center virtual sites. As a proof of concept, we have re-derived a complete set of parameters for 109 small organic molecules, and assessed the accuracy by comparing computed liquid properties with experiment. QUBEKit gives highly competitive results when compared to standard transferable force fields, with mean unsigned errors of 0.024 g/cm3, 0.79 kcal/mol and 1.17 kcal/mol for the liquid density, heat of vaporization and free energy of hydration respectively. This indicates that the derived parameters are suitable for molecular modelling applications, including computer-aided drug design.

Funding

EPSRC EP/R010153/1 and EP/L015552/1

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

Version Notes

Revisions made to introduction and further data added.

Licence

Exports