Effect of degree of unsaturation of fatty acids on the activity of FabI (enoyl-acyl carrier protein reductase) enzyme from Plasmodium falciparum: an enzoinformatics study

ObjectiveTo elucidate molecular interactions of enoyl-acyl carrier protein reductase (FabI) with unsaturated fatty acids such as docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, octadecatrienoic acid, stearic acid and arachic acid to investigate the inhibitory activities of degree of unsaturation.MethodsDocking between these ligands and enzymes were performed using Autodock4.2.ResultsDocosahexaenoic acid (a polyunsaturated fatty acid) is more efficient inhibitor of enoyl-acyl carrier protein reductase (FabI) compared to other unsaturated fatty acids with lesser double bonds and saturated fatty acid with reference to ΔG and Ki values. Hydrophobic interactions play an important role in the correct positioning of these fatty acids within the catalytic site of FabI enzyme to permit docking.ConclusionsIt has been also observed that not only the degree of unsaturation affects the antiplasmodial activity, but the length of carbon chain also plays an important role in their inhibitory activity. Such information may aid in the design of versatile FabI-inhibitors.