Binding mechanism of SARS-CoV-2 spike protein with human ACE2 receptor*

SARS-CoV-2 virus interacts via Cterminal domain of spike protein to human cell receptor protein hACE2.Amino acid residues residing at the interface play vital role in binding of SARS-CoV-2 CTD to hACE2.The detailed atomic level investigation of interactions at binding interface of SARS-CoV-2CTD hACE2 provides indispensable information on better understanding of location for drug target. In the present work, we have studied the dynamical behaviour of the complex by analyzing the molecular dynamics (MD) trajectories.The major interacting residues of SARS-CoV-2CTD and hACE2 have been identified by analyzing the nonbonded interactions such as hydrogen bondings, salt bridges, hydrophobic interactions, van der Waals interactions etc. Umbrella sampling method has been used to estimate the binding free energy for in-depth understanding of binding mechanism between virus protein and host receptor. The binding free energy difference, key residues at the interface,important atomic interactions and contact surface areas have been compared with the molecular complex of SARSCoV and hACE2. Relatively larger contact surface area, more non-bonded interactions as well as greater binding free energy provide the evidence for favorable binding of SARSCoV-2 with hACE2 receptor than SARS-CoV.