Author

Shana Bergman

Date of Award

2016

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Shipman, Steven

Area of Concentration

Computational Biochemistry

Abstract

AIDS is an epidemic that relies on the high mutation rate of HIV-1. The most promising means of combating this virus is to prevent a poorly understood process known as uncoating, where the protective capsid shell dissociates to release the infectious material. To capitalize on this opportunity to prevent infection, this research approximates the capsid's potential using a coarse grained elastic network model and then systematically perturbs each residue in the capsomer, evaluating its effect on the global potential. A simulation of this complexity and magnitude has not been approached in this way, so it was significant to prove the effectiveness of this method. The findings from perturbations were then analyzed to identify which residues are critical to the overall stability of the capsid and therefore provide potential targets for drug binding and mutation that would prevent the proper uncoating of the capsid. Many residues were identified that agreed with previous experimental findings. Other residues have been proven as regions that are critical for conferring stability and flexibility to the capsid, occurring mainly in the CTD and hexamer-hexamer interfaces.

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