Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study

Acetylcholinesterase (AChE) is a key enzyme responsible for terminating nerve impulses by hydrolyzing the neurotransmitter acetylcholine (ACh). The inhibition of AChE has gained attention as a therapeutic strategy for neurological disorders including Lewy body dementia and Alzheimer’s disease. This study investigated the effects of natural compounds on the intrinsic deformability of human AChE through computational biophysical analysis, utilizing methods such as classical dynamics, elastic networks, statistical potentials, energy frustration, and volumetric cavity analyses. The findings indicate that cyanidin significantly alters the flexibility and rigidity of AChE, particularly affecting the distribution and volume of its internal cavities, in contrast to model inhibitors like TZ2PA6. This distinct biophysical-molecular mechanism demonstrated by cyanidin highlights its potential as a target for future research and the development of new treatments for neurodegenerative diseases.