Date of Graduation

5-2023

Document Type

Thesis

Degree Name

Bachelor of Science in Chemistry

Degree Level

Undergraduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Moradi, Mahmoud

Committee Member/Reader

Sakon, Josh

Committee Member/Second Reader

Ceballos, Ruben

Committee Member/Third Reader

Stauss, Kim

Abstract

Hemagglutinin is a protein on the surface of Human Influenza Viruses.1 It is composed of two glycopolypeptide domains, the HA1 and HA2 domains. Previous studies have found that across different strains of Influenza viruses, HIS435 residues remain conserved.4 In studies where mutations occurred in hinge-site histadine residues, the Influenza virus was inactive.4 These investigations indicated a significant role of HIS435 (hinge-site histadines) in virulence. Four systems were created using Molecular dynamics (MD) simulations. Each system was composed of an Isolated HA2 trimer solvated in a 150 mM NaCl rectangular water box at 310 K under isobaric and isothermal conditions . Conditions after endosomal acidification were simulated in two of the systems by protonating their HIS435 residues. Two systems remained with neutral HIS435 residues to simulate conditions before endosomal acidification. This experimental model was implemented to study the role of HIS435 on the mechanistic change in HA2 after endosomal acidification. The simulations were run for one microsecond. During this timeframe, all systems exhibited small-scale conformational changes, however a large-scale conformational change was not observed. This investigation is a continuation of previous research which had studied the microsecond-level conformational change of the full Hemagglutinin protein as it relates to pH and hinge histidine protonation states using molecular dynamics simulations.

Keywords

pH, Influenza, HA2, H3N2, Hinge

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