Abstract
Direct dynamics calculations employing hybrid quantum mechanical and molecular mechanical (QM/MM) potentials and molecular dynamics simulation methods have been used to explore the important dynamic role that enzyme structure has on proton transfer in the C-H bond breakage of a methylamine substrate by methylamine dehydrogenase (MADH). Canonical variational transition state theory with optimised multidimensional tunnelling corrections has been used to predict deuterium kinetic isotope effects corresponding to a range of enzyme conformations and to show the importance of donor-acceptor separation, and transition state and product stabilisation within the active site. Large kinetic isotope effects can be predicted for proton transfer with both semi-empirical and ab initio electronic structure methods.
| Original language | English |
|---|---|
| Pages (from-to) | 223-242 |
| Number of pages | 19 |
| Journal | Faraday Discussions |
| Volume | 122 |
| DOIs | |
| Publication status | Published - 2002 |
Keywords
- Enzyme functional sites (active; deuterium kinetic isotope effect in methylamine dehydrogenase catalyzed reactions can reveal about reaction rate, transition state, conformations and proton transfer through proton tunneling); Bond (carbon-hydrogen; proton of carbon-hydrogen bond in methylamine is involved in proton tunneling in methylamine dehydrogenase catalyzed reactions); Proton transfer; Transition state structure (deuterium kinetic isotope effect in methylamine dehydrogenase catalyzed reactions can reveal about reaction rate, transition state, conformations and proton transfer through proton tunneling); Isotope effect (deuterium; deuterium kinetic isotope effect in methylamine dehydrogenase catalyzed reactions can reveal about reaction rate, transition state, conformations and proton transfer through proton tunneling); Enzyme kinetics (kinetic parameters of isotope effect of methylamine dehydrogenase)