1. Improving Small Molecule Force Fields by Identifying and Characterizing Small Molecules with Inconsistent Parameters
- Author
-
Victoria T. Lim, Daisy Y. Kyu, Caitlin C. Bannan, David L. Mobley, Nam Thi, and Jordan N. Ehrman
- Subjects
Models, Molecular ,Computer science ,Medicinal & Biomolecular Chemistry ,Pipeline (computing) ,Molecular Conformation ,Molecular modeling ,Chemical ,Energy minimization ,01 natural sciences ,Molecular mechanics ,Article ,Physical Phenomena ,Databases ,Medicinal and Biomolecular Chemistry ,Structure-Activity Relationship ,Models ,Theoretical and Computational Chemistry ,0103 physical sciences ,Drug Discovery ,Conformer comparison ,Molecule ,Physical and Theoretical Chemistry ,Organic Chemicals ,Aza Compounds ,010304 chemical physics ,Force field (physics) ,Molecular ,Force fields ,Atomic coordinates ,Function (mathematics) ,Potential energy ,Small molecule ,0104 chemical sciences ,Computer Science Applications ,010404 medicinal & biomolecular chemistry ,Molecular mechanics simulations ,Quantum Theory ,Thermodynamics ,Geometry optimization ,Biological system ,Databases, Chemical ,Software - Abstract
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.
- Published
- 2020