Abstract
Plasmodium falciparum
is the most lethal malaria parasite.
P. falciparum
Hsp70 (
Pf
Hsp70) is an essential molecular chaperone (facilitates protein folding) and is deemed a prospective antimalarial drug target. The present study investigates the binding capabilities of select plant derivatives, iso-mukaadial acetate (IMA) and ursolic acid acetate (UAA), against
P. falciparum
using an
in silico
docking approach. The interaction between the ligands and
Pf
Hsp70 was evaluated using plasmon resonance (SPR) analysis. Molecular docking, binding free energy analysis and molecular dynamics simulations were conducted towards understanding the mechanisms by which the compounds bind to
Pf
Hsp70. The molecular docking results revealed ligand flexibilities, conformations and positions of key amino acid residues and protein-ligand interactions as crucial factors accounting for selective inhibition of Hsp70. The simulation results also suggest protein-ligand van der Waals forces as the driving force guiding the interaction of these compounds with
Pf
Hsp70. Of the two compounds, UAA and IMA bound to
Pf
Hsp70 within the micromolar range based on surface plasmon resonance (SPR) based binding assay. Our findings pave way for future rational design of new selective compounds targeting
Pf
Hsp70.