Computational exploration of natural product inhibitors against mutant Plasmodium falciparum DHFR through pharmacophore modeling, docking, and MD simulations

Key Points

• Natural product inhibitors effectively target Plasmodium falciparum DHFR, showing promising binding affinities.
• The best-performing compounds exhibit binding energies as low as -9.8 kcal/mol against the mutant DHFR enzyme.
• Molecular docking and MD simulations were performed to analyze inhibitor interactions with DHFR over 100 nanoseconds.
• The findings suggest a pathway for developing new treatments for malaria, but biological validation is necessary.