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 journalArticle

7320 Citations (Scopus)

Abstract

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
Volume25
Issue number9
DOIs
StatePublished - Jul 15 2004

Fingerprint

Amber
Force Field
Testing
Nucleic acids
Nucleic Acids
Molecules
Energy
Halogens
RMS Errors
Pharmaceutical Preparations
Drug products
Drug Design
Pharmaceuticals
Gases
Mean Square
Proteins
Atoms
Charge
Roots
Heuristics

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)
  • Safety, Risk, Reliability and Quality

Cite this

Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., & Case, D. A. (2004). Development and testing of a general Amber force field. Journal of Computational Chemistry, 25(9), 1157-1174. https://doi.org/10.1002/jcc.20035

Development and testing of a general Amber force field. / Wang, Junmei; Wolf, Romain M.; Caldwell, James W.; Kollman, Peter A.; Case, David A.

In: Journal of Computational Chemistry, Vol. 25, No. 9, 15.07.2004, p. 1157-1174.

Research output: Contribution to journalArticle

Wang, J, Wolf, RM, Caldwell, JW, Kollman, PA & Case, DA 2004, 'Development and testing of a general Amber force field', Journal of Computational Chemistry, vol. 25, no. 9, pp. 1157-1174. https://doi.org/10.1002/jcc.20035
Wang, Junmei ; Wolf, Romain M. ; Caldwell, James W. ; Kollman, Peter A. ; Case, David A. / Development and testing of a general Amber force field. In: Journal of Computational Chemistry. 2004 ; Vol. 25, No. 9. pp. 1157-1174.
@article{d49ab71aab314556abe2b6392d80e247,
title = "Development and testing of a general Amber force field",
abstract = "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 {\AA}, which is comparable to that of the Tripos 5.2 force field (0.25 {\AA}) and better than those of MMFF 94 and CHARMm (0.47 and 0.44 {\AA}, 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 {\AA} and 1.2 kcal/mol, respectively. These data are comparable to results from Parm99/RESP (0.16 {\AA} 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.",
keywords = "Additive force field, Force field parameterization, General AMBER force field, Restrained electrostatic potential (RESP)",
author = "Junmei Wang and Wolf, {Romain M.} and Caldwell, {James W.} and Kollman, {Peter A.} and Case, {David A.}",
year = "2004",
month = "7",
day = "15",
doi = "10.1002/jcc.20035",
language = "English (US)",
volume = "25",
pages = "1157--1174",
journal = "Journal of Computational Chemistry",
issn = "0192-8651",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

TY - JOUR

T1 - Development and testing of a general Amber force field

AU - Wang, Junmei

AU - Wolf, Romain M.

AU - Caldwell, James W.

AU - Kollman, Peter A.

AU - Case, David A.

PY - 2004/7/15

Y1 - 2004/7/15

N2 - 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.

AB - 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.

KW - Additive force field

KW - Force field parameterization

KW - General AMBER force field

KW - Restrained electrostatic potential (RESP)

UR - http://www.scopus.com/inward/record.url?scp=2942532422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942532422&partnerID=8YFLogxK

U2 - 10.1002/jcc.20035

DO - 10.1002/jcc.20035

M3 - Article

C2 - 15116359

AN - SCOPUS:2942532422

VL - 25

SP - 1157

EP - 1174

JO - Journal of Computational Chemistry

JF - Journal of Computational Chemistry

SN - 0192-8651

IS - 9

ER -