Specific interactions between M. tuberculosis CYP130 and its inhibitors: Molecular simulations using ab initio fragment molecular orbital method

Tuberculosis remains a major global health problem caused by Mycobacterium tuberculosis. Cytochrome P450 enzymes such as CYP130 have an intimate involvement in pathogenesis of tuberculosis. It was demonstrated that azole compounds such as econazole and clotrimazole display inhibitory potential against the latent and multidrug-resistant forms of tuberculosis. Here we investigate the specific interactions between CYP130 and econazole as well as our proposed azole ligands at atomic and electronic levels, using ab initio molecular simulations. The specific interactions between CYP130 and ligand are investigated by ab initio fragment molecular orbital calculations at an electronic level, in order to highlight which residues of CYP130 and which parts of ligand are important for the binding between CYP130 and ligand. Based on the results, we attempt to propose novel potent inhibitors that have a strong binding affinity to CYP130.