MATCH: An atom‐typing toolset for molecular mechanics force fields

TLDR

The authors present MATCH, a toolset for automatically assigning atom types and force‑field parameters for organic molecules in molecular mechanics simulations. MATCH converts diverse chemical file formats into a molecular graph and uses a customizable pattern‑matching engine to assign atom types, charges, and parameters by comparing fragments, enabling integration with CHARMM and other force fields. Cross‑validation shows MATCH accurately reproduces CHARMM36 parameters and that bond‑charge increment rules transfer across force fields, while leave‑one‑out tests confirm missing parameters can be substituted, and the tool successfully typed, parameterized, and minimized one million PubChem molecules. © 2011 Wiley Periodicals, Inc.

Abstract

Abstract We introduce a toolset of program libraries collectively titled multipurpose atom‐typer for CHARMM (MATCH) for the automated assignment of atom types and force field parameters for molecular mechanics simulation of organic molecules. The toolset includes utilities for the conversion of multiple chemical structure file formats into a molecular graph. A general chemical pattern‐matching engine using this graph has been implemented whereby assignment of molecular mechanics atom types, charges, and force field parameters are achieved by comparison against a customizable list of chemical fragments. While initially designed to complement the CHARMM simulation package and force fields by generating the necessary input topology and atom‐type data files, MATCH can be expanded to any force field and program, and has core functionality that makes it extendable to other applications such as fragment‐based property prediction. In this work, we demonstrate the accurate construction of atomic parameters of molecules within each force field included in CHARMM36 through exhaustive cross validation studies illustrating that bond charge increment rules derived from one force field can be transferred to another. In addition, using leave‐one‐out substitution it is shown that it is also possible to substitute missing intra and intermolecular parameters with ones included in a force field to complete the parameterization of novel molecules. Finally, to demonstrate the robustness of MATCH and the coverage of chemical space offered by the recent CHARMM general force field (Vanommeslaeghe, et al., J Comput Chem 2010, 31, 671), one million molecules from the PubChem database of small molecules are typed, parameterized, and minimized. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011