KatG protein analysis: Misfolding and drug resistance

Tuberculosis is caused by Mycobacterium tuberculosis and is commonly treated with antibiotics. Recently, drug resistance to isoniazid, the most common drug utilized to treat tuberculosis, has been becoming more prevalent. Hence, this study aimed to analyze factors affecting isoniazid resistance using a bioinformatics pipeline. The KatG gene sequence was obtained from NCBI and variants from UniProt, which then underwent domain analysis, 2D and 3D structure analysis, molecular docking, and molecular dynamics. The Ramachandran plot was used to highlight the domain analysis. Molecular docking results show that the resistant variant with KatG mutation had a higher binding affinity, which was odd since a decrease in medication efficiency should result in a lower binding affinity. The visualization of the docking was discussed in detail, along with the molecular dynamic simulation.