Biophysical characterization of the SARS-CoV2 spike protein binding with the ACE2 receptor explains increased COVID-19 pathogenesis

Ratul Chowdhury; Costas D Maranas

We used the three-dimensional atomic coordinates of the experimentally determined human ACE2 (hACE2) in complex with SARS-CoV-2 spike RBD (PDB id: 6ZLG https://www.rcsb.org/structure/6lzg) as a backbone template to repackage the updated residue side-chains of feline, canine, bovine, equine, and chicken ACE2. A python script was prepared to execute multiple times the iTasser program 15 . First, a fragment structure assembly was performed using replica-exchange Monte Carlo 16 followed by clustering of decoy ACE2 structures generated using the SPICKER protocol 17 . Finally atomic-level backbone and side chain refinement was performed using fragment-guided molecular dynamics simulations (FG-MD) 18 for 50ns for each structure. All five ACE2s were subsequently docked with the SARS-CoV-2 spike RBD protein whose 3D coordinates were downloaded from the hACE2-spike complex (PDB id: 6LZG).