In Silico Study of miR-132 with mRNA of Acetylcholinesterase to Investigate the Binding Affinity for Interaction

Abstract

Acetylcholinesterase (AChE) is a key enzyme in central nervous system which hydrolaze neurotransmitter acetylcholine (ACh) at cholinergic brain synapses. High expression of AChE in brain and muscles is responsible for diverse neurological conditions leading from neuromuscular, neurodegenerative and neuropsychological diseases. miRNA-132 is a non-coding RNA molecule which help to regulate the expression level of number of genes involved in neurological development, angiogenesis and synaptic transmission. However, miR-132 is the only miR so far that has been experimentally validated as targeting AChE, with consequences on inflammatory responses. Various bioinformatics tools like MODELLER, I-Tasser, ModeRNA, 3D-Dart, ERRAT, ProSA and Rampage were employed for AChE, miR-132 and mRNA model building and their validations. The binding affinities of these macromolecules were also investigated. The results revealed that the miR-132 binds to 3'-UTR region of AChE. The catalytic triad Ser-203, His-447 and Glu-334 found in active site gorge of protein binds to the ligand. Thus, the models of proteinligand and mRNA-miR-132 complexes proved miR-132 as an inhibitor of Acetylcholinesterase. Therefore miR-132 can be a potent inhibitor for Acetylcholinesterase and further analysis of this inhibitor could be helpful for exploration of ligand binding pockets and designing of a novel therapeutic target to cure central nervous system disorders.