- Title
- The effect of Afrocentric missense variations on the structural dynamics of CYP2B6
- Creator
- Govender, Shaylyn Ashley
- Subject
- CYP2B6
- Subject
- Structural dynamics
- Subject
- Metabolism
- Subject
- Missense mutation
- Subject
- Molecular dynamics
- Date Issued
- 2025-04-02
- Date
- 2025-04-02
- Type
- Academic theses
- Type
- Master's theses
- Type
- text
- Identifier
- http://hdl.handle.net/10962/479108
- Identifier
- vital:78261
- Description
- Cytochrome P450s are a superfamily of enzymes with over 50 members involved in metabolizing 90% of xenobiotics. Among the these, families 1, 2, and 3 are responsible for approximately 80% of clinical drug metabolism. This study investigates the effect of Afrocentric missense variants on the structural dynamics of CYP2B6. Molecular dynamic simulations reveal that specific variants affect the enzyme’s flexibility and stability, potentially altering catalytic activity and drug binding properties. These findings highlight the importance of considering genetic variants in personalized medicine and drug development. By investigating CYP2B6’s function and structural changes induced by missense variants, this research advances our understanding of the enzyme’s role in drug metabolism. The study utilized computational tools such as GROMACS and AMBER for pre- and post-simulation analysis, with clustering and DSSP used to assess protein structures. Variants I328T, K282R, P428T and R140Q exhibited significant deviations in enzyme dynamics, while other variants caused minor shifts. Overall, the findings provide insight into the relationship between genetic variants and enzyme function, contributing to bioinformatics and molecular modelling approaches in drug discovery. Future studies could explore the structural and fuctional impacts of CYP2B6 bound to substrates such as antimalarials, expanding the investigation to a broader range of missense variants.
- Description
- Thesis (MSc) -- Faculty of Science, Biochemistry, Microbiology and Bioinformatics, 2025
- Format
- computer
- Format
- online resource
- Format
- application/pdf
- Format
- 1 online resource (123 pages)
- Format
- Publisher
- Rhodes University
- Publisher
- Faculty of Science, Biochemistry, Microbiology and Bioinformatics
- Language
- English
- Rights
- Govender, Shaylyn Ashley
- Rights
- Use of this resource is governed by the terms and conditions of the Creative Commons "Attribution-NonCommercial-ShareAlike" License (http://creativecommons.org/licenses/by-nc-sa/2.0/)
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | GOVENDER-MSC-TR25-32.pdf | 4 MB | Adobe Acrobat PDF | View Details Download |