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

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TitleCHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields.
Publication TypeJournal Article
Year of Publication2010
AuthorsVanommeslaeghe, K, Hatcher, E, Acharya, C, Kundu, S, Zhong, S, Shim, J, Darian, E, Guvench, O, Lopes, P, Vorobyov, I, Mackerell, AD
JournalJ Comput Chem
Volume31
Issue4
Pagination671-90
Date Published2010 Mar
ISSN1096-987X
KeywordsComputer Simulation, Models, Chemical, Models, Molecular, Molecular Dynamics Simulation, Pyrrolidines, Quantum Theory, Software
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 "all-CHARMM" simulations on drug-target interactions thereby extending the utility of CHARMM force fields to medicinally relevant systems.

DOI10.1002/jcc.21367
Alternate JournalJ Comput Chem
PubMed ID19575467
PubMed Central IDPMC2888302
Grant ListR01 GM070855 / GM / NIGMS NIH HHS / United States
R01 CA120215-04 / CA / NCI NIH HHS / United States
GM51501 / GM / NIGMS NIH HHS / United States
HL082670 / HL / NHLBI NIH HHS / United States
R01 GM051501-13 / GM / NIGMS NIH HHS / United States
R21 HL082670-01A2 / HL / NHLBI NIH HHS / United States
R01 CA107331 / CA / NCI NIH HHS / United States
GM070855 / GM / NIGMS NIH HHS / United States
CA107331 / CA / NCI NIH HHS / United States
CA120215 / CA / NCI NIH HHS / United States
R01 CA120215 / CA / NCI NIH HHS / United States
R01 GM070855-04 / GM / NIGMS NIH HHS / United States
R01 GM051501 / GM / NIGMS NIH HHS / United States
R29 GM051501 / GM / NIGMS NIH HHS / United States
R21 HL082670 / HL / NHLBI NIH HHS / United States
R01 CA107331-04 / CA / NCI NIH HHS / United States