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 A, which is comparable to
that of the Tripos 5.2 force field (0.25 A) and better than those of MMFF 94 and CHARMm
(0.47 and 0.44 A, 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 A and 1.2 kcal/mol, respectively. These data are comparable to results from
Parm99/RESP (0.16 A 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.
Copyright 2004 Wiley Periodicals, Inc.