The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor

Esther S. Brielle; Dina Schneidman-Duhovny; Michal Linial

The MD simulations were performed with GROMACS 2020 software (28) using the CHARMM36m force field (29) . Each of the complexes was solvated in transferable intermolecular potential with 3 points (TIP3P) water molecules and ions were added to equalize the total system charge. The steepest descent algorithm was used for initial energy minimization until the system converged at Fmax < 1,000 kJ/(mol · nm). Then water and ions were allowed to equilibrate around the protein in a two-step equilibration process. The first part of equilibration was at a constant number of particles, volume, and temperature (NVT). The second part of equilibration was at a constant number of particles, pressure, and temperature (NPT). For both MD equilibration parts, positional restraints of k = 1,000 kJ/(mol · nm 2 ) were applied to heavy atoms of the protein, and the system was allowed to equilibrate at a reference temperature of 300 K, or reference pressure of 1 bar for 100 ps at a time step of 2 fs. Following equilibration, the production simulation duration was 100 nanoseconds with 2 fs time intervals. Altogether 10,000 frames were saved for the analysis at intervals of 10 ps. We superimposed several MD snapshots on the recently submitted to the PDB x-ray structure (6VW1, resolution 2.7Å) of COVID-19-ACE2 complex. The average RMSD over the interface Ca atoms is ~1Å. Interaction scores between the virus spike RBD and ACE2 were calculated for each frame of the trajectory using the SOAP statistical potential (16) . In the interface contact analysis, a residue-residue contact was defined based on the inter-atomic distance, with a cutoff of 4Å. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.10.986398 doi: bioRxiv preprint