Genetic Variability of Human Angiotensin-Converting Enzyme 2 (hACE2) Among Various Ethnic Populations

Quan Li; Zanxia Cao; Proton Rahman

Molecular dynamics (MD) simulation which is a canonical method for investigating the influences of mutant on protein structure, was then applied. As mutations N638S and N720 are far away from the RBD, as a result we mainly focused on the K26R as MD simulations demonstrated that this variant mutated more frequently in Non-Finnish European while I468V mutated frequently more in East Asians. The initial wild type structure of the human ACE2 (hACE2) was selected from the X-ray crystal complex structure between hACE2 with SARS-CoV-2 spike (S) protein from Protein Data Bank15 (PDB ID: 6LZG). The initial structures of mutants were constructed using FoldX (http://foldxsuite.crg.eu/command/PositionScan). The structural minimizations and molecular dynamics simulation was performed using the GROMACS 2018.416-18 software package. OPLS-AA force field was adopted for the protein complex and the SPCE water model for solvate the system. The periodic boundary conditions (PBC) in a cubic box was applied, and the distance to the edge of the box was set as 1.0 nm. After the protein complex system was solvated, the appropriate numbers of sodium and chloride ions were added to neutralize the system. Equilibration simulations were done under the NVT ensemble for 2 ns and then the NPT ensemble for 1 ns after an extensive energy minimization by using the steepest descent algorithm. The simulation time step was 2 fs.