Binding mechanism of different variants of SARS-CoV(-2) virus with hACE2 receptor protein*

We have investigated the binding mechanism of different variants of SARS-CoV(-2) virus with hACE2 receptor protein. Understanding binding mechanism of different variants of SARS-CoV-2 virus with its receptor is essential for designing effective drug/vaccine for this virus. Classical molecular dynamics (MD) simulation has been carried out for the purpose. In our study, three important binding regions between different variants of SARS-CoV(-2) and hACE2 have been identified. Further relative strengths of binding of different variants of SARS-CoV(-2) virus with hACE2 have been estimated via study of hydrogen bonding, salt bridges, electrostatics and van der Waals interactions. The average number of hydrogen bonds in wild type, delta, mu and omicron variants are estimated to be 7, 7, 5 and 5 respectively. We have also estimated binding free energy for wild type, delta, mu and omicron variants with hACE2 by MM/GBSA method and the values are - 44.15 ± 8.07 kcal/mol, - 44.93 ± 7.69 kcal/mol, - 37.31 ± 7.98 kcal/mol and -36.20 ± 7.61 kcal/mol respectively. Moreover estimation of free energy by Umbrella sampling for wild type and delta variants shows the higher free energy of binding for the delta variants than the wild type.