Force Field Development
The following are some resources to facilitate the development of empirical force field parameters for use with the CHARMM 22 and 27 biomolecular force fields. For small organic molecules, we refer to the CHARMM General Force Field (CGenFF). The optimization of new parameters for CHARMM is not difficult, however, it does require careful reading of one of the parameter papers to understand the methodology. I suggest the supplemental information for the CHARMM 27 nucleic acid parameter paper, for which PDF versions are below. In addition, there is a tutorial available from a workshop that Dr. C. Brooks III and myself gave a couple years ago at the Pittsburgh Supercomputing Center along with a powerpoint presentation from the 2003 Sanibel conference that goes over creating a topology and obtaining parameters for a drug-like molecule. Links are provided below. The Pittsburgh site includes a collection of example CHARMM input files for parameter development.
Below are PDF files of the Supplemental Information from the CHARMM27 nucleic acids parameter optimization paper (Foloppe, N. and MacKerell, Jr., A.D. Journal of Computational Chemistry 21: 86-104, 2000. This represents the complete parameter paper, as in the published version the methods section is omitted (the best part...). Note that for the adjustment of the partial atomic charges it is important that the QM interactions with water be calculated at the HF/6-31G* level of theory to ensure compatibility with the current CHARMM force fields. For QM calculations to determine geometries, vibrations or conformational energies, use the highest level of theory possible.
An overview of the parameter optimization approaches to extend the CHARMM force fields may be found at the CHARMM Links/Forum Link or from the following reference:
MacKerell, A.D., Jr. "Atomistic Models and Force Fields" in Computational Biochemistry and Biophysics, O.M. Becker, A.D. MacKerell, Jr., B. Roux and M. Watanabe, Eds., Marcel Dekker, Inc. New York, 2001, p. 7-38. See the following link: http://www.dekker.com/servlet/product/productid/0455-X