Molecular basis for the enantioselective binding of a novel class of cytochrome bc1 complex inhibitors

The recently solved co-crystal structures of mitochondrial cytochrome bc1 complex with inhibitors have provided an important structural framework for the elucidation of modes of binding of various bc1 complex inhibitors. N-Phenyl triazolones, a novel class of bc1 complex ubiquinol oxidation (Qo)-site inhibitors, were found to exhibit atropisomerism; in few cases, the atropisomers were resolved and shown to express different biological activities. However, the underlying mechanism for such differential binding of the enantiomers to bc1 complex is unknown. Here molecular docking is used to examine the binding modes of the N-phenyl triazolones fungicides. Our docking studies allow the molecular basis for the enantioselective binding of atropisomeric triazolones to be elucidated. Furthermore, the mode of binding of azoxystrobin has also been clarified.