Identifying PF11_0189 from <i>Plasmodium falciparum</i> as a Potential Target for Antimicrobial Peptides with Antimalarial Properties: Insights from Molecular and Kinetic Studies

Abstract P. falciparum , responsible for the deadliest form of malaria, has shown increasing resistance to traditional antimalarial drugs, necessitating new therapeutic approaches. This study identifies PF11_0189, a putative metalloprotease from P. falciparum , as a potential target for various antimicrobial peptides (AMPs). Using molecular docking, molecular dynamics (MD) simulations, and enzyme kinetics, we assessed the binding and inhibitory effects of these AMPs on PF11_0189. Docking results revealed strong binding affinities, with binding energies ranging from −8.6 to −14.8 kcal/mol for AMPs such as Defensin, Dermaseptin S4, and PcFK1. MD simulations demonstrated stable interactions, with RMSD values consistently around 2–3 Å for key complexes, indicating PF11_0189′s structural compatibility as a target. Enzyme kinetics further confirmed this, showing significant inhibition of PF11_0189 activity by Defensin and PcFK1, which reduced Vmax by up to 18% and exhibited low Ki values of 0.45 µM and 0.41 µM, respectively. These results highlight PF11_0189 as a viable target of AMPs, suggesting its crucial role in the antimalarial activity of these peptides. By elucidating the molecular interactions between AMPs and PF11_0189, this study provides valuable insights into developing novel AMP‐based therapies to combat drug‐resistant malaria.