A transferable double exponential potential for condensed phase simulations of small molecules

06 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The Lennard-Jones potential is the most widely-used function for the description of non-bonded interactions in transferable force fields for the condensed phase. This is not because it has an optimal functional form, but rather it is a legacy resulting from when computational expense was a major consideration and this potential was particularly convenient numerically. At present, it persists because the effort that would be required to re-write molecular modelling software and train new force fields has, until now, been prohibitive. Here, we present smirnoff-plugins as a flexible framework to extend the Open Force Field software stack to allow custom force field functional forms. We deploy smirnoff-plugins with the automated Open Force Field infrastructure to train a transferable, small molecule force field based on the recently-proposed double exponential functional form, on over 1000 experimental condensed phase properties. Extensive testing of the resulting force field shows improvements in transfer free energies, with acceptable conformational energetics, run times and convergence properties compared to state-of-the-art Lennard-Jones based force fields.


Force field
Double exponential
Open source software
Open Force Field
Molecular mechanics
Free energy
Drug discovery

Supplementary materials

Supporting Information for: A transferable double exponential potential for condensed phase simulations of small molecules
Buckingham 6-8 potential information, change in force field parameters on optimisation, water model analysis, test set statistics, convergence data, computational details (PDF).


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.