Dinitrogen Activation and Electron and Proton Delivery in the Nitrogenase Complex
EMSL Project ID
51913
Abstract
We are requesting EMSL supercomputing resources to tackle the mechanism of electron and proton delivery to dinitrogen (N2) to yield ammonia (NH3) in the Mo-dependent nitrogenase -- biological nitrogen fixation. Nitrogenases are a major component of the biological nitrogen cycle and provides the bioavailable nitrogen nutrient that supports more than half the human population. In recent years, thanks to the generous support from EMSL, our team in collaboration with Seefeldt (Utah State University) and Hoffman (Northwestern University) has revealed key features of the nitrogenase catalytic mechanism. In particular, we performed an extensive analysis of the thermodynamics of binding and activation of N2 takes place after the accumulation of four electron and for proton in the catalytic FeMo-cofactor, with the concomitant reductive elimination of H2.We propose to expand these investigations by using large-scale QM/MM free energy simulations to understand how protons and electrons are delivered to the active site of Mo-dependent nitrogenase, providing critical insight into both (1) the modulation of the active site chemistry by the surrounding residues and (2) the interplay of this chemistry with the large-scale conformational dynamics of the protein complex.
Specifically, we will explore: (i) how the flexibility of 96Arg modulates the migration of the hydrides on the surface of the FeMo-co in the E4 state; (ii) how the flexibility of the terminal residue of the proton delivery pathway (195His) regulates proton delivery to both FeMo-co and N2; (iii) how the hemilability of the cofactor Fe-S bonds modulates N2 activation. We will characterize the relative free energy of the possible states, and a variety of thermodynamic and electrochemical properties, such as metal cluster redox potentials, hydride donor ability of the FeMo-co Fe atoms, and pKa values of ionizable residues at the active site.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2021-10-01
End Date
2023-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members