CO2 activation and conversion by the CODH/ACS enzymatic complex
EMSL Project ID
51914
Abstract
The purpose of the proposal is to computationally characterize the key biochemical and biophysical features of carbon monoxide dehydrogenase (CODH) and acetyl-coenzyme A synthase (ACS) enzymatic complex. This complex catalyzes the conversion of CO2 to CO and the subsequent condensation of CO with a methyl intermediate and coenzyme A to form acetyl-coenzyme A. We aim to understand the factors regulating substrate binding, CO2 and CO activation, and reaction pathways. These include metal coordination chemistry, active site residues directly interacting with the catalytic center, and ultimately the entire protein.The theoretical investigation of the CO2 and CO activation by the CODH/ACS complex requires the ability to obtain reliable structural, spectroscopic, electrochemical, reactivity and free energy information for systems of high complexity. We will obtain this information using long-timescale molecular dynamics simulations, and large-scale QM/MM free energy simulations. Specific issues we will address: (i) the driving force for CO/CO2 binding to the Ni centers; (ii) the correlation between the metal centers oxidation states and CODH/ACS chemistry; (iii) the role of the interactions at the active site during C-O and C-C bond breaking or formation; (iv) the structural and electronic determinants that modulate the redox properties of the catalytic metal clusters; (v) the role of the metal clusters flexibility and protein dynamics. Hypotheses elaborated on the basis of our calculations will be tested against experimental assays performed by Ragsdale at the University of Michigan Ann Arbor.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2021-10-01
End Date
2023-10-01
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members