Poisson Statistical Method to Quantify the Specific Binding Force Between S Spike Protein and ACE2

Angiotensin-converting enzyme 2 (ACE2) is widely acknowledged as a primary receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells. Elucidating the details of the interaction between ACE2 and S spike protein of SARS-CoV-2 molecule has significance to understand the mechanisms of COVID-19 disease. The binding force between the two has been estimated using molecular dynamics simulation and measured using force spectroscopy at the molecular scale under experimental conditions. Considering the complicated situations of cellular membrane, the binding of S spike protein and ACE2 on cell membrane differs from that observed under molecular in vitro conditions. In this paper, we measured the binding force between the S spike protein and molecules on cellular membrane mimicking virus infection using atomic force microscopy (AFM) molecular force spectroscopy. We then estimated the binding force of a single pair of S spike proteins and ACE2 molecules using Poisson statistical methods. Our results of a single pair of molecular binding forces between S spike protein and ACE2 is consistent with previous reports. Overall, our study utilizes the Poisson statistical approach to estimate the binding force between S spike proteins and ACE2 molecules during virus infection of cells for the first time.