Differences between Dimerized and Monomeric ACE2 Models on Extracellular TMPRSS2 and SARS-CoV-2 Spike Wild Type Binding Using a SETS-QAOA-MaxCut and ZDOCK Workflow

Angiotensin-converting enzyme 2 (ACE2) has been identified as the top binding target for the SARS-CoV-2 Spike protein, with transmembrane-bound serine protease type 2 (TMPRSS2) being a close second, as TMPRSS2 cleaves the dimerization between the collectrin and metallocarboxypeptidase regions of ACE2. While Protein Data Bank (PDB) models such as 1R42 do represent most of the ACE2 structure and has been widely used in models of SARS-CoV-2 Spike + ACE2 models, only recent structures, such as the B and D chains of PDB 6M18, show this collectrin portion of ACE2. We checked binding differences of (PDB 6VSB) SARS-CoV-2 Spike Wild Type to different ACE2 PDBs, as well as extracellular TMPRSS2 (PDB 7MEQ). We hypothesized that SARS-CoV-2 Spike and TMPRSS2 bind better to ACE2 with collectrin. We used a quantum algorithm to prune PDBs, followed by ZDOCK binding, and then contact/clash validation. We found that the ZDOCK Scores after pruning for 1R42 and 6VSB was 1588.281, while the score for 6M18 and 6VSB was 2952.885. 7MEQ may bind better to 1R42 than 6M18, with a 7MEQ-1R42 score of 2372.075 and a 7MEQ-6M18 score of 2087.073. While 7MEQ binds 6M18 at the neck region and 6VSB to the collectrin, 7MEQ binds 1R42 at a less consequential amino acid (GLN 287).