Molecular Docking and Dynamic Simulation with ADMET Exploration of Natural Products Atlas Compound Library to search for Potential Alpha Amylase Inhibitors for the T۲DM Treatment

One of the major global causes of early mortality and illness is diabetes. Diabetes mellitus, a global metabolic condition, affects almost every age group in the world's population. The primary cause of diabetes is insufficient pancreatic function, which occurs when the organ fails to produce enough insulin or fails to adequately use the insulin it produces. The aim of this study is to identify a lead drug as a potent alpha-amylase inhibitor to fight T۲DM. We determine the pharmacological alpha amylase target (PDB ID: ۳BAX) through extensive analyses and reviews of the available literature. We used a pharmacophore query to search the Natural Products Atlas library for a potent inhibitor. The PyRx version of AutoDock Vina is utilized for the docking process. We use the Desmond software to identify the stability of complexes in physiological environments. According to our analysis, the primary substances NPA۰۱۶۶۸۹ and NPA۰۱۱۵۶۵ are potent inhibitors against alpha-amylase (۳BAX). After determining the lead, we identified the NPA۰۱۶۶۸۹ and NPA۰۱۱۵۶۵ compounds as the most reactive, with binding affinities of -۹.۳ kcal/mol and -۹.۲ kcal/mol, respectively. TYR_A:۶۲, TYR: A_۱۵۱, LYS: A_۲۰۰, HIS: A_۲۰۱, ILE: A_۲۳۵, and HIS: A_۳۰۵ residues critically interacted with the NPA۰۱۶۶۸۹ ligand. Similarly with ligand NPA۰۱۱۵۶۵, the binding residues were TRP: A_۵۹, THR: A_۱۶۳, LEU_A:۱۶۵, ARG: A_۱۹۵, ASP_A:۱۹۷_A:۱۹۸, GLU: A_۲۳۳, and HIS: A_۲۹۹. This study concluded that NPA۰۱۶۶۸۹ and NPA۰۱۱۵۶۵ have the potential to modulate the activity of alpha-amylase enzyme, making them potential lead molecules for the design or development of additional anti-alpha-amylase compounds.

Keywords:

T۲DM , Alpha Amylase , Molecular Dynamics , Computational screening , lead discovery