FFParam-v2.0: A Comprehensive Tool for CHARMM Additive and Drude Polarizable Force-Field Parameter Optimization and Validation

Developing production quality CHARMM force-field (FF) parameters is a very detailed process involving a variety of calculations many of which are specific for the molecule of interest. The first version of FFParam was developed as a standalone python package designed for optimization of electrostatic and bonded parameters of the CHARMM additive and polarizable Drude FFs using quantum mechanical (QM) target data. The new version of FFParam has multiple new capabilities for FF parameter optimization and validation, with emphasis on the ability to use condensed phase target data in the optimization. FFParam-v2 allows optimization of Lennard-Jones (LJ) parameters using potential energy scans of interactions between selected atoms in a molecule and noble gases viz. He, Ne and through condensed phase calculations from which experimental observables such as heats of vaporization and free energies of solvation may be obtained. This functionality serves as a gold-standard for both optimizing parameters and validating the performance of the final parameters. A new bonded parameter optimization algorithm has been introduced to account for simultaneously optimizing multiple molecules sharing parameters. FFParam-v2 also supports comparison of normal modes and the percent contribution of internal coordinates towards each normal mode obtained from QM and molecular mechanics calculations. Such comparison capability is vital to validate the balance amongst various bonded parameters that contribute to the complex normal modes of molecules. User interaction has been extended beyond the original graphical user interface (GUI), to include command line interface capabilities that allows for integration of FFParam in workflows thereby facilitating automation of parameter optimization. With these new functionalities, FFParam is a more comprehensive parameter optimization tool for both beginner and advanced users.