Date of Award

2022-05-01

Degree Name

Master of Science

Department

Computational Science

Advisor(s)

Lin L. Lin

Abstract

Dengue virus causes serious diseases and considerable deaths each year all around the globe. Dengue virus undergoes assembly in a capsid, matures and becomes viral. Revealing mechanisms of the viral capsid protein may lead to the discovery of novel drugs that prevent this assembly to happen and stop the virus from spreading. Here I present a computational work which is focused on the stability and assembly of the dengue viral capsid. The E and M proteins conform a heterotetramer, which consists of two copies of E and M proteins. The heterotetramers form a highly ordered capsid. In the electrostatic analysis it was identified four binding modes among two heterotetramers that repeat periodically in the virus capsid. In each binding mode I performed a salt bridge calculation, electrostatic potential surface calculation, electrostatic force calculation and a molecular dynamics simulation. Among the four binding modes, heterotetramers in binding modes I, II and IV showed to be attractive. Surprisingly, binding mode III has a repulsive interaction, making it a potential target for drug design. Furthermore, to obtain a more detailed description of the capsid assembly, I studied the folding energy and pH dependence of binding energy in a E protein homodimer. The pH dependence analysis showed that the E protein homodimer binding energy is low and independent from pH in a range of 6 to 10. Therefore, it might be possible that due to this wide range of pH survival in the dengue virus capsid, the virus can be spread fast and survive all around the world. Overall, this study shows that using computational approaches to study the electrostatic features of dengue virus capsid assembly is a promising direction that might lead to the development of novel drugs against the disease caused by dengue virus.

Language

en

Provenance

Received from ProQuest

File Size

38 p.

File Format

application/pdf

Rights Holder

Alan Eduardo Lopez Hernandez

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Included in

Biophysics Commons

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