Catalytic Mechanism of Dihydrofolate Reductase Enzyme. A Combined Quantum-Mechanical/Molecular-Mechanical Characterization of Transition State Structure for the Hydride Transfer Step
✍ Scribed by Castillo, R.; Andrés, J.; Moliner, V.
- Book ID
- 115466477
- Publisher
- American Chemical Society
- Year
- 1999
- Tongue
- English
- Weight
- 154 KB
- Volume
- 121
- Category
- Article
- ISSN
- 0002-7863
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We used molecular dynamics simulation and free energy Ž . perturbation FEP methods to investigate the hydride-ion transfer step in the Ž . mechanism for the nicotinamide adenine dinucleotide phosphate NADPHdependent reduction of a novel substrate by the enzyme dihydrofolate reductase Ž . DHFR . The
A theoretical study is presented of the catalytic mechanism of dihydrofolate reductase (DHFR) enzyme based upon the characterization of the transition structure (TS) for the hydride transfer step. Analytical gradients at AM1 and PM3 semiempirical levels have been used to characterize the saddle poin