A comparative molecular docking study of curcumin and methotrexate to dihydrofolate reductase.

Abstract

Interaction of curcumin (CUR) with the enzyme dihydrofolate reductase (DHFR) was studied by molecular docking using AutoDock 4.2 as the docking software application. AutoDock 4.2 software serves as a valid and acceptable docking application to study the interactions of small compounds with proteins. Interactions of curcumin with DHFR were compared to those of methotrexate (MTX), a known inhibitor of the enzyme. The calculated free energy of binding (ΔG binding) shows that curcumin (ΔG = -9.02 kcal/mol; Ki = 243 nM) binds with affinity comparable to or better than MTX (ΔG = -8.78 kcal/mol; Ki = 363 nM). Binding interactions of curcumin with active site residues of the enzyme are also predicted. Curcumin appears to bind in a bent conformation making extensive VDW contacts in the active site of the enzyme. Hydrogen bonding and pi-pi interaction with key active site residues are also observed. Thus, curcumin can be considered as a good lead compound in the development of new inhibitors of DHFR, which is a potential target of anti-cancer drugs. The results of these studies can serve as a starting point for further computational and experimental studies.