Docking Studies, ADMET prediction of phytochemical inhibitors for Alzheimer’s disease

ABSTRACT: Alzheimer's disease (AD) is one form of senile dementia that gradually increases over time. It affects memory, thinking, and behaviour. The occurrence of Alzheimer’s disease is directly linked with a deficiency in the brain neurotransmitter acetylcholine. Acetylcholinesterase, also known as AChE, is an enzyme that degrades (through its hydrolytic activity) the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic synapses in the central nervous system. Acetylcholinesterase (AChE) inhibitors are one of the most actively investigated classes of compounds in the search for effective treatment of Alzheimer's disease. The most common used cholinesterase inhibitors (drug) in Alzheimer's disease are rivastigmine, galantamine, and donepezil. The protein sequence of Acetylcholinesterase with accession number P22303 was obtained from UniProt and the 3D structure was modelled by Modeller. Docking was performed with the available drugs for Acetylcholinesterase as well as with the phytochemicals obtained from PubChem, Dr Duke’s phytochemical library and literature mining.

Keywords: Modeller; Acetylcholinesterase; Alzheimer disease; Molegro Virtual Docker; Phytochemicals

摘要：阿尔茨海默病（AD）是一种随着年龄增长逐渐加剧的老年痴呆症形式，它影响记忆、思维和行为。阿尔茨海默病的出现与大脑神经递质乙酰胆碱的缺乏直接相关。乙酰胆碱酯酶，亦称AChE，是一种通过其水解活性降解神经递质乙酰胆碱的酶，产生胆碱和乙酸基团。该酶主要存在于中枢神经系统的神经肌肉接头和胆碱能突触中。乙酰胆碱酯酶（AChE）抑制剂是寻找阿尔茨海默病有效治疗方法中最积极研究的化合物类别之一。在阿尔茨海默病中，最常用的胆碱酯酶抑制剂（药物）包括利凡斯明、加兰他敏和多奈哌齐。具有访问号P22303的乙酰胆碱酯酶蛋白序列从UniProt获得，其三维结构由Modeller建模。对乙酰胆碱酯酶的现有药物以及从PubChem、Dr Duke的植物化学库和文献挖掘获得的植物化学物质进行了对接实验。
关键词：Modeller；乙酰胆碱酯酶；阿尔茨海默病；Molegro Virtual Docker；植物化学物质