Repurposing molecular docking software to identify likely resistance-causing mutations in QcrA and QcrB from Mycobacterium tuberculosis.

Burgess, J.*, Cloete, R.

SANBI, University of the Western Cape

Telacebec (Q203) is a novel anti-tubercular drug that has successfully completed phase IIa clinical trials. Q203 targets QcrB, a protein component of the electron transport chain of Mycobacterium tuberculosis. To evaluate the future efficacy of the drug in the treatment of Tuberculosis, we have assessed the possible single mutations that could arise in QcrB, and whether they may cause resistance to Q203. The total number of mutations assessed is 16908. For each mutant, the protein structure for QcrB was modified, energy minimized, then simulated with the drug Q203 to see whether there were significant changes in the binding between Q203 and the mutated protein target.

Keywords: Autodock Vina, resistance mutations, tuberculosis, CHPC, protein structures