Ali_2024_J.Recept.Signal.Transduct.Res__1

Cerebral amyloid plaques in the brain define the elderly neuralgic disorder, Alzheimer's disease (AD). The enzyme Acetylcholinesterase (AChE) was reported to play a vital role in AD. It was shown that AChE induces amyloid fibril formation forming highly toxic AChE-Amyloid-beta (Abeta) complexes. AChE can accelerate amyloid formation, and its inhibition could prevent such alterations to the enzyme. Understanding the proteostasis of AChE and its binding site to cellular chaperone GRP78 (Glucose-regulated protein 78) would help find a treatment for AD. In this study, the state of the art computational tools were utilized to predict the binding location of AChE that can stably associate with the cellular chaperone, GRP78. Sequence comparison along with molecular docking predicts two binding locations on AChE (C69-C96 and C257-C272) that could bind to GRP78 substrate binding domain beta (SBDbeta). The analysis of the docking data suggests that the former location has the best average binding affinity value (-12.16 kcal/mol) and average interaction pattern (13.9 +/- 3.5 H-bonds, 5.5 +/- 1.4 hydrophobic contacts, and 1.4 +/- 1.2 salt bridges).