Computational methods for the study of enzymic reaction mechanisms: 1. Application to the hydride transfer step in the catalysis of dihydrofolate reductase

Peter L. Cummins; Stephen P. Greatbanks; Alistair P. Rendell; Jill E. Gready

doi:10.1021/jp021070q

Computational methods for the study of enzymic reaction mechanisms: 1. Application to the hydride transfer step in the catalysis of dihydrofolate reductase

Peter L. Cummins, Stephen P. Greatbanks, Alistair P. Rendell, Jill E. Gready^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

The computational methods for the study of enzymic reaction mechanisms were discussed. High level quantum mechanics cluster calculations and hybrid semiempirical calculations were used for enzymic reactions. The effects of active site protonation on the hydride ion transfer reaction from the nicotinamide adenine dinucleotide phosphate (NADPH) cofactor to the substrate folate and dihydrofolate in the presence of the enzyme, dihydrofolate reductase from Escherichia coli (E.coli) were analyzed. It was concluded that the reduction takes place when active site (Asp 27) (E.coli) was protonated.

Original language	English
Pages (from-to)	9934-9944
Number of pages	11
Journal	Journal of Physical Chemistry B
Volume	106
Issue number	38
DOIs	https://doi.org/10.1021/jp021070q
Publication status	Published - 26 Sept 2002

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title = "Computational methods for the study of enzymic reaction mechanisms: 1. Application to the hydride transfer step in the catalysis of dihydrofolate reductase",

abstract = "The computational methods for the study of enzymic reaction mechanisms were discussed. High level quantum mechanics cluster calculations and hybrid semiempirical calculations were used for enzymic reactions. The effects of active site protonation on the hydride ion transfer reaction from the nicotinamide adenine dinucleotide phosphate (NADPH) cofactor to the substrate folate and dihydrofolate in the presence of the enzyme, dihydrofolate reductase from Escherichia coli (E.coli) were analyzed. It was concluded that the reduction takes place when active site (Asp 27) (E.coli) was protonated.",

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Computational methods for the study of enzymic reaction mechanisms: 1. Application to the hydride transfer step in the catalysis of dihydrofolate reductase. / Cummins, Peter L.; Greatbanks, Stephen P.; Rendell, Alistair P. et al.
In: Journal of Physical Chemistry B, Vol. 106, No. 38, 26.09.2002, p. 9934-9944.

Research output: Contribution to journal › Article › peer-review

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AU - Rendell, Alistair P.

AU - Gready, Jill E.

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AB - The computational methods for the study of enzymic reaction mechanisms were discussed. High level quantum mechanics cluster calculations and hybrid semiempirical calculations were used for enzymic reactions. The effects of active site protonation on the hydride ion transfer reaction from the nicotinamide adenine dinucleotide phosphate (NADPH) cofactor to the substrate folate and dihydrofolate in the presence of the enzyme, dihydrofolate reductase from Escherichia coli (E.coli) were analyzed. It was concluded that the reduction takes place when active site (Asp 27) (E.coli) was protonated.

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Computational methods for the study of enzymic reaction mechanisms: 1. Application to the hydride transfer step in the catalysis of dihydrofolate reductase

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