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) |
|---|---|
| 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 |
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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
Cite this
CHARMM general force field : A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. / Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.; Kundu, S.; Zhong, S.; Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; Vorobyov, Igor; Mackerell, A. D.
In: Journal of Computational Chemistry, Vol. 31, No. 4, 01.03.2010, p. 671-690.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CHARMM general force field
T2 - A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields
AU - Vanommeslaeghe, K.
AU - Hatcher, E.
AU - Acharya, C.
AU - Kundu, S.
AU - Zhong, S.
AU - Shim, J.
AU - Darian, E.
AU - Guvench, O.
AU - Lopes, P.
AU - Vorobyov, Igor
AU - Mackerell, A. D.
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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.
AB - 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.
KW - Computational chemistry
KW - Computer aided drug design
KW - Drug design
KW - Empirical force field
KW - Medicinal chemistry
KW - Molecular dynamics
KW - Molecular modeling
UR - http://www.scopus.com/inward/record.url?scp=76249087938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76249087938&partnerID=8YFLogxK
U2 - 10.1002/jcc.21367
DO - 10.1002/jcc.21367
M3 - Article
C2 - 19575467
AN - SCOPUS:76249087938
VL - 31
SP - 671
EP - 690
JO - Journal of Computational Chemistry
JF - Journal of Computational Chemistry
SN - 0192-8651
IS - 4
ER -