Probing potential antimalarial compounds through molecular docking of Plasmodium falciparum protein Pf12p
Keywords:
Malaria, Pf12p, molecular docking, natural products, manzamine A, antimalarial drug discovery, bioactive compoundsAbstract
Background: Malaria remains a critical global health challenge, with Plasmodium falciparum posing a significant threat due to its evolving drug resistance. Targeting crucial parasite proteins offers a promising strategy for novel antimalarial development. Pf12p, involved in DNA repair, emerges as a potential target due to its essential role and relatively conserved structure.
Methods: This study employed molecular docking to screen a library of 23 compounds, including natural products, for their interaction with Pf12p. Binding energies, inhibition constants, and 2D/3D visualizations of ligand-protein complexes were analyzed.
Results: Manzamine A, a natural compound, exhibited the most favorable binding affinity to Pf12p, showcasing its potential as a potent antimalarial agent. Docking results for N-Acetylglucosamine (NAG), the original ligand in the Pf12p crystal structure, validated the methodology. Visualizations revealed specific amino acid and functional group interactions driving ligand binding.
Conclusion: Our study identified promising antimalarial candidates, particularly manzamine A, targeting Pf12p. By integrating natural products, validating with existing ligands, and utilizing detailed visualizations, we demonstrate the potential of molecular docking for antimalarial drug discovery. Further research is necessary to validate efficacy and safety in vitro and in vivo. This study contributes valuable insights towards the development of targeted and resilient antimalarial treatments.
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