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Improving Small Molecule Force Fields by Identifying and Characterizing Small Molecules with Inconsistent Parameters

submitted on 22.08.2020, 18:46 and posted on 24.08.2020, 09:16 by Jordan Ehrman, Victoria T. Lim, Caitlin C. Bannan, Nam Thi, Daisy Kyu, David Mobley
Many molecular simulation methods use force fields to help model and simulate molecules and their behavior in various environments. Force fields are sets of functions and parameters used to calculate the potential energy of a chemical system as a function of the atomic coordinates. Despite the widespread use of force fields, their inadequacies are often thought to contribute to systematic errors in molecular simulations. Furthermore, different force fields tend to give varying results on the same systems with the same simulation settings. Here, we present a pipeline for comparing the geometries of small molecule conformers. We aimed to identify molecules or chemistries that are particularly informative for future force field development because they display inconsistencies between force fields. We applied our pipeline to a subset of the eMolecules database, and highlighted molecules that appear to be parameterized inconsistently across different force fields. We then identified over-represented functional groups in these molecule sets. The molecules and moieties identified by this pipeline may be particularly helpful for future force field parameterization.


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University of California, Irvine


United States

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Declaration of Conflict of Interest

DLM is a member of the Scientific Advisory Board of OpenEye Scientific Software and an Open Science Fellow with Silicon Therapeutics.