Date of Graduation

5-2023

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology (MS)

Degree Level

Graduate

Department

Biological Sciences

Advisor/Mentor

Mahmoud Moradi

Committee Member

Douglas D Rhoads

Second Committee Member

Dylan Girodat

Third Committee Member

Bin Dong

Keywords

Coronavirus;COVID-19 variants;Electrostatic interaction;Molecular dynamics simulation;Protein;SARS-CoV

Abstract

The SARS-related coronavirus (SARS-rCoV) is a highly contagious virus that has raised significant worldwide health concerns. It caused outbreaks in 2002-2003 and more recently in 2019-2020 with SARS-CoV-2. SARS-CoV-2 is responsible for the COVID-19 pandemic, which has resulted in a significant global impact on health and the economy. The spike protein of the virus plays a critical role in its infectivity and transmission, and the receptor-binding domain (RBD) within the spike protein is of particular interest, as it is responsible for binding to the human angiotensin-converting enzyme 2 (ACE2) receptor. In this study, we used Molecular dynamics (MD) simulations to investigate the electrostatic interaction patterns in the active and inactive models of SARS-CoV-1, SARS-CoV-2, and several variants of SARS-CoV-2, including the Alpha, Beta, Delta, and Epsilon variants. MD simulations are a computational method that allows us to model the motion of atoms and molecules over time, providing insights into the structure and behavior of biological molecules. The findings indicate differential electrostatic interaction patterns between the RBD of SARS-CoV-1 and SARS-CoV-2 spike protein. The RBD of SARS-CoV-2 exhibited a slower conformational pattern, which could influence higher stability, potentially affecting its binding affinity with the ACE2 receptor. Additionally, the Delta variant demonstrated significant differences in electrostatic interactions compared to the original SARS-CoV-2 strain, particularly in the N-terminal domain (NTD) and RBD regions. These findings suggest that Delta variant mutations could affect the RBD’s binding affinity to the ACE2 receptor, impacting transmission and virulence. Overall, this study highlights electrostatic interaction patterns in SARS-CoV-1, SARS-CoV-2, and variants, with implications for the development of long-term effective vaccines and therapeutics. Understanding the spike protein’s molecular basis may enable designing more effective treatments and strategies to prevent the spread of these viruses.

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