In silico analysis of Glycogen synthase kinase 3-beta (GSK-3β) as aflatoxin binder

Abstract

Aflatoxins are secondary metabolites of certain fungi like Aspergillus flavus, Aspergillus niger, Aspergillus nomius and Aspergillus parasiticus. Food products like cereals, milk, milk products, nuts, oilseeds and spices are reported for aflatoxins contamination. Among the fourteen aflatoxin types reported so far, aflatoxins B1, B2, G1, G2, M1, and M2 are commonly studied. Aflatoxins are known to cause various diseases including aflatoxicosis in livestock and domestic animals and cancer in humans. Recently aflatoxin B1 has reported binding with Glycogen synthase kinase 3-beta (GSK-3β). This prompted to carry out the present study, where Glycogen synthase kinase 3-beta (GSK-3β) was evaluated on the docking behaviour of 13 aflatoxin analogues using Patch Dock. In addition, molecular physicochemical, drug-likeness, ADME (Absorption, Distribution, Metabolism and Excretion analyses) were also carried out. The molecular physiochemical analysis revealed that aflatoxin analogue showed nil violation and complied well with the Lipinski’s rule of five. ADME analysis indicates all thirteen aflatoxin analogue predicated to have high gastro-intestine (GI) absorption property. Docking studies, with GSK-3β, revealed that aflatoxin G2 analogue showed the largest atomic contact energy (-224.82 kcal/mol) and Aflatoxin P1 analogue had the least (-160.33 kcal/mol). In addition, aflatoxin P1 analogue has interacted with Asp200 amino acid residue of GSK-3β. Thus, the present study showed the potential of GSK-3β as aflatoxin binder.