Interaction Analysis on the SARS-CoV-2 Spike Protein Receptor Binding Domain Using Visualization of the Interfacial...

Area of Science:

• Structural biology
• Computational chemistry
• Immunology

Background:

• Protein-protein interactions are crucial for biological processes.
• Understanding these interactions is key to drug discovery and disease mechanisms.
• The SARS-CoV-2 spike protein's interaction with ACE2 is central to viral entry.

Purpose of the Study:

• To introduce and demonstrate the Visualization of Interfacial Electrostatic Complementarity (VIINEC) method.
• To analyze the electrostatic interactions in the SARS-CoV-2 spike protein's receptor-binding domain (RBD) with ACE2 and a neutralizing antibody (B38).
• To elucidate the role of specific residues, like E484, in protein-protein binding.

Main Methods:

• Utilized the Visualization of Interfacial Electrostatic Complementarity (VIINEC) technique.
• Calculated electrostatic potentials (ESP) using the ab initio fragment molecular orbital method.
• Examined the molecular interactions at the protein-protein interface of RBD/ACE2 and RBD/B38 complexes.

Main Results:

• VIINEC identified local electrostatic complementarity between RBD's E484 and ACE2.
• A considerable repulsive electrostatic interaction was observed involving E484.
• Significant differences in the electrostatic potential map were found between the RBD/ACE2 and RBD/B38 interfaces.

Conclusions:

• VIINEC is an effective method for visualizing electrostatic complementarity in protein-protein interactions.
• The E484 residue plays a complex role in the electrostatic interaction with ACE2.
• Differences in electrostatic potential maps correlate with antibody specificity, offering insights into antibody-target recognition mechanisms.