Computational Biology Methods Devising Site-Directed Mutagenesis Reactions of the Polymerase Acidic Protein for the Enhancement of Protein Solubility

Authors

Presenter(s)

Juliano V. Aquilino

Comments

Presentation: 3:40 p.m.-4:00 p.m., Kennedy Union 311

Files

Description

Current treatments of an Influenza infection target frequently mutating surface proteins. This causes increased variability in the effectiveness of modern treatment methods, as a single mutation in the protein could cause the antiviral to be ineffective. A component of the RNA-dependent-RNA-polymerase (RdRp) of the Influenza A virus, Polymerase Acidic (PA) protein, is a promising antiviral target for a new generation of Influenza treatments because of its highly conserved nature. PA has been shown to have a similar structure and sequence across known strains of Influenza. Drug design research utilizes crystal structure to synthetically improve viral inhibitors through in silico analysis that can prevent the binding of PA to an additional protein, Polymerase Basic 1 (PB1). However, to gain a crystal structure of the protein for drug design, the macromolecule needs to be soluble, and previous experiments have shown highly insoluble characteristics of the PA protein. Computational calculations were utilized to create a set of site-directed mutagenesis reactions that would theoretically enhance the solubility of the protein structure by optimizing the intramolecular and intermolecular interactions. The investigated mutations are intended to decrease aggregation propensity, increase solubilizing interactions, increase solvent exposure, and increase the stability of the protein under expression conditions. Following the completion of the experiments, it was shown that residue-specific mutations of PA slightly increased the solubility of the protein structure under experimental conditions.

Publication Date

4-20-2022

Project Designation

Independent Research

Primary Advisor

Douglas S. Daniels

Primary Advisor's Department

Chemistry

Keywords

Stander Symposium project, College of Arts and Sciences

Recommended Citation

"Computational Biology Methods Devising Site-Directed Mutagenesis Reactions of the Polymerase Acidic Protein for the Enhancement of Protein Solubility" (2022). Stander Symposium Projects. 2456.
https://ecommons.udayton.edu/stander_posters/2456