SARS-CoV-2 spike RBD ACE2

SARS-CoV-2 spike RBD ACE2 models and predicts interactions between SARS-CoV-2 spike protein receptor binding domain (RBD) variants and the human ACE2 receptor to assess how RBD amino acid substitutions affect binding affinity.

Key Features:

• 3D Comparative Modeling: Constructs three-dimensional comparative models of spike RBD–ACE2 protein complexes for characterized variants of concern and interest including B.1.1.7, P.1, B.1.351, B.1.427/B.1.429, B.1.141, B.1.617.1, and B.1.620.
• Interaction Energy Prediction: Calculates interaction energies at the spike RBD–ACE2 protein–protein interface from the 3D models to assess the effects of mutations on binding affinity.
• Mutation Analysis: Screens mutation databases and performs localization analysis within the RBD "boat-shaped" receptor binding motif, highlighting stern, bow, and hull regions where substitutions alter interaction energies.
• Identification of Alternative Receptors: Evaluates structural similarity to identify alternative host proteins such as THOP1 and NLN that may interact with the spike protein in tissues with low ACE2 expression.

Scientific Applications:

• Predicting Transmissibility and Virulence: Assess how RBD substitutions modulate ACE2 binding affinity to inform predictions of variant transmissibility and virulence.
• Preventing Outbreaks: Prioritize variants with increased predicted binding affinity for surveillance and outbreak risk assessment.
• Guiding Therapeutic Development: Inform therapeutic and receptor-targeting strategies by characterizing ACE2 and alternative receptor interactions.

Methodology:

Computational comparative 3D modeling and simulation of spike RBD–ACE2 complexes, calculation of interaction energies from those models, and integration of mutation database screening and localization analysis.