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 (?G binding) shows that curcumin (?G = -9.02 kcal/mol; Ki = 243 nM) binds with affinity comparable to or better than MTX (?G = -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.

SUBMITTER: Hobani Y 

PROVIDER: S-EPMC5450246 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature