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 language | English (US) |
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Pages (from-to) | 671-690 |
Number of pages | 20 |
Journal | Journal of Computational Chemistry |
Volume | 31 |
Issue number | 4 |
DOIs | |
State | Published - Mar 1 2010 |
Externally published | Yes |
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