This project is aimed at characterizing the interactions of SARS-CoV-2 Spike protein and its variants with multiple full-length antibodies and monitoring the accompanying conformational dynamics. Different categories of antibodies are tested that recognize different domains of the Spike protein. The project aims at identifying the effects of weak, moderate and strong neutralizing antibodies on Spike protein and decipher their mechanisms of action. In addition to the direct binding effects, distal allosteric effects are also determined. A range of biophysical experiments, biochemical assays, and molecular dynamics simulations are used as orthogonal approaches. The rationale is to identify regions on the SARS-CoV-2 Spike protein that acts as indicators for antibody binding and use these hotspots to develop better neutralizing antibodies against SARS-CoV-2 and any future viral pandemics.