Molecular Dynamics Simulation Study on Stabilities and Reactivities of NADH Cytochrome B5 Reductase

Abstract

Binding free energies between coenzyme (FAD and NADH) and the apoenzyme of NADH-cytochrome b5 reductase (b5R) were estimated by applying the continuum Poisson-Boltzmann (PB) model to structures sampled from molecular dynamics simulations in explicit water molecules. Important residues for the enzymatic catalysis were clarified using a computational alanine scanning method. The binding free energies calculated by applying an alanine scanning method can successfully reproduce the trends of the measured steady-state enzymatic activities kcatNADH/KmNADH. Significant decreases in the binding free energy are expected when one of the four residues Arg91, Lys110, Ser127, and Thr181 is mutated into Ala. According to the results of the molecular dynamics simulation, Thr181 is considered to be one of the key residues that helps NADH to approach the isoalloxazine in FAD. Finally, we have constructed very simplified model systems and carried out density functional theory calculations using B3LYP/LANL2DZ//ROHF(or RHF)/LANL2DZ level of theory in order to elucidate a realistic and feasible mechanism of the hydride-ion transfer from NADH to FAD affected by HEME(Fe3+) as an electron acceptor. Our calculated results suggest that the electron and/or hydride-ion transfer reaction from NADH to FAD can be accelerated in the presence of HEME(Fe3+).

Theoretical study on the absorption spectra of fac-Ir(ppy)3 in the amorphous phase of organic electro-luminescent devices

“…In the present investigation, quantum mechanical/molecular mechanical (QM/ MM) MD simulations [21,22] were performed and the interaction energies between Ir(ppy) 3 and specific CBP molecules were analyzed. We report here some interesting results for the absorption spectra of Ir(ppy) 3 in the amorphous CBP layer.…”

Spin–orbit coupling analyses of phosphorescent processes in Ir(Zppy)3 (Z = NH2, NO2 and CN)

“…Such interactions are the targets in another series of our investigations. [87][88][89][90][91][92] On the basis of these successes, the substituent effects in bis [2-(phenyl)…”

Role of tryptophan residues of Erv1: Trp95 and Trp183 are important for its folding and oxidase function

“…MD simulations of the WT and Erv1 W95F mutant were performed using AMBER12 [ 29 ] with the protein modelled by the AMBER ff99SB force field [ 30 ] and the substrate FAD represented using the parameters and partial charges developed by Asada et al [ 31 ]. The initial protein co-ordinate was taken from the crystal structure of the C-terminal core domain (CTD) of Erv1 from Saccharomyces cerevisiae at 2.0 Å (1 Å=0.1 nm) resolution (PDB code: 4E0H) [ 11 ].…”