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Molecular Dynamics Simulation Studies to Probe the Impact of Oxidative Stress on the Binding of SARS-CoV-2 Spike Protein to Angiotensin-Converting Enzyme II

Bethany Laatsch, Harrison Lowater, Leo Lonzarich, Carl Fossum, Alex Narkiewicz-Jodko, Sanchita Hati, and Sudeep Bhattacharyya, Department of Chemistry and Biochemistry, University of Wisconsin - Eau Claire, 105 Garfield Ave, Eau Claire, WI 54701

The receptor-binding domain of the SARS-CoV-2 spike protein as well as the human cell surface receptor angiotensin-converting enzyme II (ACE2) contain several cysteine residues. These cysteine residues exist either in the form of disulfide bridges (oxidized) or as thiols (reduced). The thiol-to-disulfide equilibrium is shifted to the right when there are excess reactive oxygen species (ROS) in the body, which is referred to as oxidative stress. It has been shown that certain preexisting conditions associated with oxidative stress such as diabetes, obesity, heart conditions, and age can put individuals at a higher risk of contracting COVID-19.  Therefore, we hypothesized that the oxidized state of these proteins may have an impact on the binding of the virus protein to the receptor. To test our hypothesis, we used molecular dynamics simulations to study the interacting residues at the binding interface of the complex formed by the receptor-binding domain of SARS-CoV-2 and the peptidase domain of ACE2. Four complexes of ACE2 and SARS-CoV-2 in different redox states were generated by either preserving the disulfides or reducing them to thiols. Molecular dynamics simulations were carried out for each protein complex over 200 ns timescale.  To analyze the changes in the key interactions and their evolutions through time, a script was created, which is capable of analyzing the simulation data and produce statistical quantities at various time scales. The preliminary data and findings of this study will be presented, which are likely to demonstrate if there exists a correlation between redox changes and the binding affinity of the SARS-CoV-2 RBD towards the human ACE2 receptor protein. 




Additional Abstract Information

Presenters: Bethany Laatsch, Harrison Lowater, Carl Fossum, Alex Narkiewicz-Jodko

Institution: University of Wisconsin - Eau Claire

Type: Poster

Subject: Biochemistry

Status: Approved


Time and Location

Session: Poster 2
Date/Time: Mon 3:00pm-4:00pm
Session Number: 2518