The free energy of the HHZn enzyme reaction path from NWChem QM/MM Simulations
EMSL Project ID
47626
Abstract
In this program we will collaborate with Marat Valiev (PNNL) to utilize the NWChem QM/MM package to simulate the free energy of the HHZn reaction path. There are a number of tasks that must be performed and will need access to a highly parallel computational environment. These are: 1. A reactive state that agrees with X-ray structures has to be identified. That means Identifying a QM and MM region in the code, equilibrating the structures and testing various ways to morph the observed inactive X-ray structure to an active state. This is our initial phase. Perhaps surprisingly there is still uncertainty here and previous calculations have not been done an accurate quantum chemistry level (B3LYP or higher).
2. Similarly we need to identify potential product state structures. While there is some agreement as to the reactive state general base (N1:G12) There are real problems with the general acid. We will have to test various choices. These will depend on the positioning and protonation of various candidates. There is also the suggestion that the general acid may be the hydrated Mg2+ ion. Compute intensive free energy calculations will be used in these calculations.
3. Potential general acid and general bases must be identified. In the HHZn enzyme the general acid may be associated with or just activated by the Mg2+. This role is difficult to justify with the present x-ray structure.
4. Reaction paths have to be identified and the possibility of a stable intermediate investigated. This will require the use of the nudged elastic band option of the software.
5. Finally the free energy variation has to be calculated for the paths identified and the barrier heights identified. The various roles of the Mg2+ ions will be investigated and the possible motion of the protons in the catalytic cell identified and correlated with the reaction processes. The heights of reaction barriers to and from the intermediate or to the single transitions state must be found.
Project Details
Project type
Limited Scope
Start Date
2012-04-25
End Date
2012-06-25
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
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