Exploring Novel Inhibitors for Babesia bigemina Lactate Dehydrogenase: A Computational Structural Biology Perspective

Babesia bigemina is an apicomplexan parasite and causes “Texas fever” in bovines. Lactate dehydrogenase (LDH) is an essential enzyme in regulating anaerobic metabolism. The presence of five amino acid insertion in the active site of many apicomplexan LDH makes a significant difference between the parasitic LDH and the host counterpart. Therefore, apicomplexan LDH is an attractive drug target. In this study, a structure-based drug discovery approach was performed to find novel inhibitor candidates. In the first round, possible candidates were identified by following the virtual screening workflow. Then, the compounds with favourable docking scores were filtered using the QM-polarized ligand docking and induced fit docking methods. As a result, 20 novel compounds that bind to the active site of the BbigLDH and have low affinity with the host LDHs have been identified. Molecular dynamics simulations of the complexes (in total 8.8 µs) were performed and binding free energies were calculated. In conclusion, compounds named C09, C16 and C18 deserve further investigation to better understand their potential therapeutic effects on babesiosis. The findings of this study, elucidating the structural properties of BbigLDH enzyme and discovering its potential inhibitors, might pave the way for further research in developing LDH-targeted therapeutic interventions.