AChE Inhibition Study for Alzheimer's Disease Treatment: An In-silico Study

Abstract

Alzheimer's disease (AD) is the most common form of dementia associated with plaques and tangles in the brain. Several acetylcholinesterase inhibitors have been clinically used to delay or halt the progression of the disease. Solanadine (Snd) and gamma solamargine (Gsm) have been shown to inhibit acetylcholinesterase (AChE). The current study attempts to describe the molecular interactions between human brain AChE and inhibitors Snd and Gsm. The free energy of binding and estimated dissociation constant (Ki) for the 'Snd-AChE Catalytic Anionic site (CAS)-interaction' were determined to be –9.51 kcal/mol and 107.54 nM, respectively and the free energy of binding and estimated Ki for the 'Gsm -AChE CAS-interaction' were determined to be – 8.64 kcal/mol and 463.88 nM, respectively. Hydrophobic interactions, polar interactions, and hydrogen bonding play an important role in the correct positioning of Snd within the 'catalytic site' of AChE to permit docking, while hydrophobic interactions and polar interactions play a significant role in the correct positioning of Gsm within the 'catalytic site' of AChE to permit docking. It is hoped that the information provided in this study will help in the design of AChE-inhibitors as anti-Alzheimer agents.