Volume 3 Supplement 1
Investigation on the reaction mechanism of ribonuclease enzymes
© Elsässer et al; licensee BioMed Central Ltd. 2009
Published: 05 June 2009
The purpose of this research program was to investigate the reaction mechanism of this enzyme using high level quantum chemistry methods of NWChem  with the highest feasible accuracy (DFT/B3LYP, Ahlrichs-pVDZ basis set) to provide an accurate representation of the chemistry of the active site (QM region) and molecular mechanics (Amber 99) to describe the remaining protein and solvent (MM region).
For this enzyme reaction there is no data providing a detailed picture of any structures along the reaction path . However, there are structural data for a vanadate complex , which has been accepted as a transition state analogue. After evaluation of our computational analysis we substituted the central vanadium by phosphorus to model the intermediate state.
Afterwards we elongated the endocyclic and exocyclic P-O bonds to find reactant and product states allowing for relaxation at each step. In addition a thermally averaged NEB method has been implemented to produce an unbiased view of the movement of atoms as the system evolves along the reaction path. Free energy calculations have been performed to account for thermal fluctuations of the protein environment. This way we could calculate the energy profile of the hydrolysis step and identify the transition state structures along the reaction coordinate.
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