Rapid parameterization of small molecules using the force field toolkit

The inability to rapidly generate accurate and robust parameters for novel chemical matter continues to severely limit the application of molecular dynamics simulations to many biological systems of interest, especially in fields such as drug discovery. Although the release of generalized versions o...

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Bibliographic Details
Published in:Journal of computational chemistry 2013-12, Vol.34 (32), p.2757-2770
Main Authors: Mayne, Christopher G., Saam, Jan, Schulten, Klaus, Tajkhorshid, Emad, Gumbart, James C.
Format: Article
Language:English
Subjects:
Algorithms
Computer Simulation
forcefields parameterization CHARMM CGenFF
Models, Molecular
Molecules
Parameter optimization
Pyrrolidines - chemistry
Quantum physics
Software
Software packages
Solvents
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Summary:The inability to rapidly generate accurate and robust parameters for novel chemical matter continues to severely limit the application of molecular dynamics 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, for example, General Amber Force Field and CHARMM General Force Field, 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, setup 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 (
ISSN:0192-8651
1096-987X
DOI:10.1002/jcc.23422