Development and testing of a general Amber force field

Junmei Wang, Romain M. Wolf, James W. Caldwell, Peter A. Kollman, David A. Case

Research output: Contribution to journalArticlepeer-review

12597 Scopus citations


We describe here a general Amber force field (GAFF) for organic molecules. GAFF is designed to be compatible with existing Amber force fields for proteins and nucleic acids, and has parameters for most organic and pharmaceutical molecules that are composed of H, C, N, O, S, P, and halogens. It uses a simple functional form and a limited number of atom types, but incorporates both empirical and heuristic models to estimate force constants and partial atomic charges. The performance of GAFF in test cases is encouraging. In test I, 74 crystallographic structures were compared to GAFF minimized structures, with a root-mean-square displacement of 0.26 Å, which is comparable to that of the Tripos 5.2 force field (0.25 Å) and better than those of MMFF 94 and CHARMm (0.47 and 0.44 Å, respectively). In test II, gas phase minimizations were performed on 22 nucleic acid base pairs, and the minimized structures and intermolecular energies were compared to MP2/6-31G* results. The RMS of displacements and relative energies were 0.25 Å and 1.2 kcal/mol, respectively. These data are comparable to results from Parm99/RESP (0.16 Å and 1.18 kcal/mol, respectively), which were parameterized to these base pairs. Test III looked at the relative energies of 71 conformational pairs that were used in development of the Parm99 force field. The RMS error in relative energies (compared to experiment) is about 0.5 kcal/mol. GAFF can be applied to wide range of molecules in an automatic fashion, making it suitable for rational drug design and database searching.

Original languageEnglish (US)
Pages (from-to)1157-1174
Number of pages18
JournalJournal of Computational Chemistry
Issue number9
StatePublished - Jul 15 2004


  • Additive force field
  • Force field parameterization
  • General AMBER force field
  • Restrained electrostatic potential (RESP)

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics


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