Computational Methods for the Study of Enzymic Reaction Mechanisms. 1. Application to the Hydride Transfer Step in the Catalysis of Dihydrofolate Reductase

Cummins, PeterGreatbanks, SRendell, AlistairGready, Jill2015-12-131520-6106http://hdl.handle.net/1885/72836The 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.Keywords: Activation energy; Catalyst activity; Computation theory; Computer simulation; Escherichia coli; Free energy; Hydrides; Ionization; Molecular dynamics; Nuclear magnetic resonance; Optimization; Probability density function; Density functional theory (DFT)Computational Methods for the Study of Enzymic Reaction Mechanisms. 1. Application to the Hydride Transfer Step in the Catalysis of Dihydrofolate Reductase200210.1021/jp021070q2015-12-11