School of Science Department of Chemistry 12 The Impact of Spike Mutations on SARS-CoV-2 Neutralization Supervisor: SU Haibin / CHEM Student: HONG Runnan / MATH-STAT Course: UROP 2100, Fall The SARS-CoV-2 spike (S) protein is a trimeric glycoprotein essential for viral entry into host cells. Glycosylation plays a critical role in stabilizing this protein, modulating its conformational transitions, and evading host immune responses. This study focuses on modeling a fully glycosylated spike protein of the Delta variant and investigating its open-close conformational dynamics using molecular dynamics (MD) simulations. The glycosylation process was performed using CHARMM-GUI, followed by solvation and forcefield preparation for MD simulations. Pulling simulations revealed the structural transitions between the receptor-binding domain (RBD) and the C-terminal domain (CTD) hinge. Early results suggest that glycosylation enhances stability and affects the conformational flexibility of the spike protein. This progress report outlines the methodology, preliminary results, and future directions for this ongoing study. The Impact of Spike Mutations on SARS-CoV-2 Neutralization Supervisor: SU Haibin / CHEM Student: LIN Sijia / CHEM Course: UROP 3100, Fall SARS-CoV-2 virus has made a severe impact in human society since 2019. Mutations on Spike glycoproteins on the virus have been claimed to affect viral infectivity. Glycosylation also plays a key role in the Spike properties, specifically on N-linked glycans. Molecular dynamic simulations are used to explore the conformational dynamics of the SARS-CoV-2 Spike glycoprotein. RMSD and position changes of RBD both show the glycoprotein’s conformation changing process. Differences in free energy pattern and in conformational structures are identified through literature comparison. Further studies will be proceeded to provide more insights into the conformational dynamics of the SARS-CoV-2 Spike glycoprotein. The Impact of Spike Mutations on SARS-CoV-2 Neutralization Supervisor: SU Haibin / CHEM Student: WOO Pok Yin / CHEM Course: UROP 1100, Spring UROP 2100, Summer Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen responsible for Coronavirus Disease 2019 (COVID-19), initiates infection by using its spike (S) glycoprotein to facilitate entry into host cells. This process occurs through the binding of the spike protein’s receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 (ACE2) receptor, a key step in viral attachment and fusion. Neutralizing antibodies (nAbs) play a critical role in immune defense by recognizing and binding to specific regions of the spike protein—particularly the RBD and the N-terminal domain (NTD)—thereby blocking viral entry. However, genetic mutations within the spike protein can alter its structure, potentially diminishing antibody recognition. Such changes may confer resistance to existing neutralizing antibodies, undermining vaccine effectiveness and heightening the risk of immune escape, which in turn facilitates sustained transmission and the emergence of new variants.
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