Interaction pattern of aldose reductase with β-glucogallin: Active site exploration and multiple docking analyses

Abstract

The search for an ideal natural drug candidate with minimal side effects has been a never-ending challenge. In diabetes, there are so many potential drug candidates; however, systematic research is necessary to put candidate molecules into effect. β-glucogallin (PubChem CID: 124021) found in Emblica officinalis is explored as a potential candidate molecule to inhibit aldose reductase activity, a key enzyme related to the microvascular complications in diabetic patients. High-resolution crystal structure of human aldose reductase (ALR2) (PDB ID: “1pwm”) from ‘Protein Data Bank’ was retrieved, and active site determination was done using “ CASTp” and blind docking strategies. “Swiss Dock” blind docking revealed a total of 13 active residues, which were found common in the five best binding modes in regard to their free binding energy. The active residues were utilized again to selectively dock β-glucogallin (PubChem CID: 124021) in “Swiss Dock” for which the average free binding energy was −8.07884 kcal/mol calculated from 5 best binding modes. Additionally, a selective docking analysis was performed in ‘Auto Dock 4.2′ using a genetic algorithm where the same binding mode was observed. The lowest binding energy calculated in Auto Dock was −17.37 kcal/mol with an inhibition constant of 186.59 fM, which is substantial to prove the efficacy of this molecule as a potential drug target. In both docking platforms, the interaction pattern stayed in the same orientation. So, this study showed the interactions pattern of β-glucogallin (PubChem CID: 124021) with tentative active sites of aldose reductase (ALR2) (PDB ID: 1pwm) in details which may open up future possibilities for treating patients with diabetic microvascular complications.