Computational structure-guided approach to simulate delamanid and pretomanid binding to mycobacterial F420 redox cycling proteins: identification of key determinants of resistance.

Abstract excerpt

The recently approved delamanid (DLM) and pretomanid (PTM) improved the existing options to treat multidrug-resistant tuberculosis (MDR-TB). However, the high spontaneous mutation rates in mycobacterial F420 genes ddn, fgd1, fbiA, fbiB, fbiC, and fbiD create a bottleneck to successful anti-TB treatments. Of known mutations, identifying the therapeutically relevant ones is a prerequisite for understanding the drug...

Topics

• Molecular Dynamics Simulation
• Nitroimidazoles
• Antitubercular Agents
• Oxazoles
• Bacterial Proteins
• Protein Binding
• Mutation
• Mycobacterium tuberculosis
• Oxidation-Reduction
• Binding Sites