Theoretical and Computational Chemistry

501Y.V2 Spike Protein Resists the Antibody in Atomistic Simulations

Son Tung Ngo Ton Duc Thang University

Abstract

SARS-CoV-2 Spike (S) protein is a major biological target for COVID-19 vaccine design. Unfortunately, recent reports indicated that Spike (S) protein mutations can lead to antibody resistance. However, understanding the process is limited, especially at the atomic scale. The structural change of S protein and neutralizing antibody fragment (FAb) complexes was thus probed using molecular dynamics (MD) simulations. In particular, backbone RMSD of the 501Y.V2 complex was significantly larger than that of the WT implying a large structural change of the mutation system. Moreover, the mean of , CCS, and SASA are almost the same when compared two complexes, but the distribution of these values are absolutely different. Furthermore, the free energy landscape of the complexes was significantly changed when the 501Y.V2 variant was induced. The binding pose between S protein and FAb was thus altered. The FAb-binding affinity to S protein was thus reduced due to revealing over steered-MD (SMD) simulations. The observation is in good agreement with the respective experiment that the 501Y.V2 SARS-CoV-2 variant can escape from neutralizing antibody (NAb).

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The first draft 1.0

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