Tackling TB in cattle: Identifying inhibitors of cell wall biosynthesis enzymes from Mycobacterium bovis
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Chemistry
Abstract
Activity assay on InhA and evaluation of a proposed inhibitor
This project involves both the preparation of the InhA enzyme and the determination of its activity using a spectrophotometric assay. Wild-type InhA from M. tuberculosis, which has been cloned into an E. coli expression vector, will be expressed and purified. The activity of the enzyme will then be determined, by monitoring the consumption of NADH using spectrophotometry. If time allows, the IC50 of a compound identified as a potential inhibitor of InhA will be determined.
Structure-based design of novel InhA inhibitors: Virtual screening
The availability of high quality 3D structures of InhA allows structure-based drug design approaches to be used in this project to identify new molecules that will inhibit this enzyme. In-silico screening of drug-like compounds will be carried out, to identify molecules that will bind effectively to InhA. In this project students will learn how to use 3D protein structures from the Brookhaven database, to carry out virtual screening of candidate drug molecules. This will involve experience using the GOLD virtual screening software, together with standard molecular graphics and modelling software. In a drug design project, inhibitor molecules identified in this way, would subsequently be tested experimentally.
This project involves both the preparation of the InhA enzyme and the determination of its activity using a spectrophotometric assay. Wild-type InhA from M. tuberculosis, which has been cloned into an E. coli expression vector, will be expressed and purified. The activity of the enzyme will then be determined, by monitoring the consumption of NADH using spectrophotometry. If time allows, the IC50 of a compound identified as a potential inhibitor of InhA will be determined.
Structure-based design of novel InhA inhibitors: Virtual screening
The availability of high quality 3D structures of InhA allows structure-based drug design approaches to be used in this project to identify new molecules that will inhibit this enzyme. In-silico screening of drug-like compounds will be carried out, to identify molecules that will bind effectively to InhA. In this project students will learn how to use 3D protein structures from the Brookhaven database, to carry out virtual screening of candidate drug molecules. This will involve experience using the GOLD virtual screening software, together with standard molecular graphics and modelling software. In a drug design project, inhibitor molecules identified in this way, would subsequently be tested experimentally.
Organisations
People |
ORCID iD |
| Neil Thomas (Primary Supervisor) |
 http://orcid.org/0000-0002-9260-5423
|
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M008770/1 | 01/10/2015 | 31/03/2024 | |||
| 1647816 | Studentship | BB/M008770/1 | 01/10/2015 | 30/09/2019 |
| Description | Compounds designed in this study were ineffective against the enzyme InhA for inhibition of tuberculosis, more work will be needed to determine whether derivatives of the structures tested could be used as inhibitors using molecular modelling as guidance. |
| Exploitation Route | Compounds designed and tested can be altered and improved upon as the core structure may still hold promise as a scaffold for InhA inhibition. |
| Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |
| Description | Presented a poster at 2nd Symposium on Medicinal Chemistry for Global Health |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Presented a poster about my research thus far at the 2nd Symposium on Medicinal Chemistry for Global Health to a range of attendees including postgraduate students, industrial leaders and other academics from institutions across the world. |
| Year(s) Of Engagement Activity | 2017 |