Christopher G. Mayne, Jan Saam, Klaus Schulten, Emad Tajkhorshid, and James C.
Gumbart.
Rapid parameterization of small molecules using the Force Field
Toolkit.
Journal of Computational Chemistry, 34:2757-2770, 2013.
(PMC: 3874408)
MAYN2013
The inability to rapidly generate accurate and robust parameters for novel chemical matter
continues to severely limit the application of molecular dynamics (MD) simulations to many
biological systems of interest, especially in fields such as drug discovery. Although the
release of generalized versions of common classical force fields, e.g., GAFF and CGenFF,
have posited guidelines for parameterization of small molecules, many technical challenges
remain that have hampered their wide-scale extension. The Force Field Toolkit (ffTK),
described herein, minimizes common barriers to ligand parameterization through
algorithm and method development, automation of tedious and error-prone tasks, and
graphical user interface design. Distributed as a VMD plugin, ffTK facilitates the traversal
of a clear and organized workflow resulting in a complete set of CHARMM-compatible
parameters. A variety of tools are provided to generate quantum mechanical target data,
set up multidimensional optimization routines, and analyze parameter performance.
Parameters developed for a small test set of molecules using ffTK were comparable to
existing CGenFF parameters in their ability to reproduce experimentally measured values
for pure-solvent properties (<15% error from experiment) and free energy of solvation
(0.5kcal/mol from experiment).
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0.5kcal/mol from experiment).
