Identifying Potential Inhibitors of the Human A-amylase Enzyme via Molecular Docking and Virtual Screening
Author(s): Nursel Eski, Cengiz Z Altuntas, Harun Yilmaz and Senol Dane*
Abstract
Background: The alpha amylase enzyme plays a critical role in starch digestion to glucose, affecting the blood glucose levels present in one’s bloodstream. Objective: Inhibition of this enzyme can, potentially, modify its catalytic activity and treat a patient with diabetes mellitus. By preventing the catalysis of the a-amylase enzyme, the rate at which carbs break down to sugar and enter the bloodstream can be reduced, decreasing the glucose in one’s bloodstream. This can be done by performing molecular docking to test the binding affinity between phytochemicals and the active site of the protein. With the right dosage and concentration, the phytochemicals with the lowest, or best, binding affinity can be considered to later produce a promising drug that goes off as oral treatment that would be taken with one’s diet to slow the reaction rate. As this study is nothing new and has been experimented on before, the goal of this project is to compare the results to those of the experimentations. Methods: By finding the binding affinity of phytochemicals with the enzyme’s active site, it can be determined which of them are favorable. These phytochemicals can be retrieved from plants that have already been scientifically proven to have effects on the human alpha-amylase enzyme. Once docking of the chemical constituents with the protein’s active site is complete, toxicity checking of the phytochemicals can be done through “mcule”. Whether or not the ran phytochemicals contain inhibiting effects can be determined by creating a threshold which is calculated by first running already- known inhibitors of this enzyme, finding their mean binding affinities, and calculating the standard deviation. Results: About 64 out of the 109 phytochemicals ran met the calculated threshold, the phytochemical Taraxasterol, from the plant Taraxacum, yielding the best binding affinity of –12.36 kcal/mol, although the toxicity checker pointed out potentially toxic parts of its structure. Oleanolic acid is a close and apparent nontoxic second, however, with a binding affinity of -11.72 kcal/mol. Conclusion: Surely, most of the phytochemicals ran have remarkable binding affinities with the active site of the alpha- amylase enzyme. This study, hypothesized and experimented on by several researchers, could have potentiality in the evolution of diabetes treatment if further carried out. By first testing out the phytochemicals with the best binding affinities in a laboratory using an assay kit, micro plate, and dosages of these phytochemicals. According to the results of the experimentation, the phytochemical with the most potential can be turned into a drug for the use of diabetes treatment. Patients with diabetes mellitus would take this medication, in the form of a pill, with their diet so that it could be put to work during the digestion process.