CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields

K. Vanommeslaeghe, E. Hatcher, C. Acharya, S. Kundu, S. Zhong, J. Shim, E. Darian, O. Guvench, P. Lopes, Igor Vorobyov, A. D. Mackerell

Research output: Contribution to journalArticlepeer-review

2482 Scopus citations

Abstract

The widely used CHARMM additive all-atom force field includes parameters for proteins, nucleic acids, lipids, and carbohydrates. In the present article, an extension of the CHARMM force field to drug-like molecules is presented. The resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical groups present in biomolecules and drug-like molecules, including a large number of heterocyclic scaffolds. The parametrization philosophy behind the force field focuses on quality at the expense of transferability, with the implementation concentrating on an extensible force field. Statistics related to the quality of the parametrization with a focus on experimental validation are presented. Additionally, the parametrization procedure, described fully in the present article in the context of the model systems, pyrrolidine, and 3-phenoxymethylpyrrolidine will allow users to readily extend, the force field to chemical groups that are not explicitly covered in the force field as well as add functional groups to and link together molecules already available in the force field. CGenFF thus makes it possible to perform "allCHARMM" simulations on drug-target interactions thereby extending the utility of CHARMM force fields to medicinally relevant systems.

Original languageEnglish (US)
Pages (from-to)671-690
Number of pages20
JournalJournal of Computational Chemistry
Volume31
Issue number4
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Keywords

  • Computational chemistry
  • Computer aided drug design
  • Drug design
  • Empirical force field
  • Medicinal chemistry
  • Molecular dynamics
  • Molecular modeling

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

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