فهرست نشریات علمی دسترسی آزاد ایران

Malaria remains a significant global health challenge, particularly in developing regions, necessitating the development of novel antimalarial agents. In this study, we employed a combination of structure-based modeling, includes molecular docking based virtual screening, molecular dynamics (MD) simulations, and pharmacokinetic evaluations on identifying potential binders targeting Plasmodium falciparum falcipain-2, a crucial protease for the parasite's survival. A re-docking approach was used to validate the docking protocol, achieving an RMSD of 1.697 Å, indicating high accuracy. The shortlisted compounds were then subjected to MD simulations over 100 ns, where their stability, flexibility, and compactness were analyzed using RMSD, RMSF, and radius of gyration (RoG) metrics. Ligands L2, L3, and L4 exhibited the most promising profiles, demonstrating strong stability, favorable binding orientations, and compatibility with the target's binding site, comparable or superior to the control ligand. Pharmacokinetic properties were assessed, and the drug-likeness of these compounds was confirmed, supporting their potential as falcipain-2 binders. This integrated approach identified promising binders that warrant further in vitro and in vivo validation for therapeutic application against P. falciparum. The methodology and findings contribute valuable insights into structure-based drug design for antimalarial compounds, offering potential approach to combat malaria effectively.