Computational Chemistry Laboratory, Institute of Chemistry, University of Brasilia, Brasilia, DF, 70910-900, Brazil.
J Mol Model. 2022 Aug 10;28(9):252. doi: 10.1007/s00894-022-05252-2.
Alzheimer disease (AD) is a neurodegenerative process, one of the most common and incident dementia in the population over 60 years. AD manifests the presence of complex biochemical processes involved in neuronal degeneration, such as the formation of senile plaques containing amyloid-β peptides, the development of intracellular neurofibrillary tangles, and the suppression of the acetylcholine neurotransmitter. In this way, we performed a set of theoretical tests of tacrine ligand and acetylcholine neurotransmitter against the human acetylcholinesterase enzyme. Molecular docking was used to understand the most important interactions of these molecules with the enzyme. Computational chemistry calculation was carried out using MP2, DFT, and semi-empirical methods, starting from molecular docking structures. We have also performed studies regarding the non-covalent interactions, electron localization function, molecular electrostatic potential and explicit water molecule influence. For Trp86 residue, we show two main interactions in accordance to the results of the literature for TcAChE. First, intermolecular interactions of the cation-π and sigma-π type were found. Second, close stacking interactions were stablished between THA+ and Trp86 residue on one side and with Tyr337 residue on the other side.
阿尔茨海默病（AD）是一种神经退行性过程，是 60 岁以上人群中最常见和最常见的痴呆症之一。AD 表现为涉及神经元变性的复杂生化过程的存在，例如含有淀粉样β肽的老年斑的形成、细胞内神经原纤维缠结的发展以及乙酰胆碱递质的抑制。 为此，我们对他克林配体和乙酰胆碱递质对人乙酰胆碱酯酶进行了一系列理论测试。 分子对接用于了解这些分子与酶的最重要相互作用。 使用 MP2、DFT 和半经验方法从分子对接结构开始进行计算化学计算。 我们还进行了关于非共价相互作用、电子定域函数、分子静电势和显式水分子影响的研究。 对于 Trp86 残基，根据 TcAChE 的文献结果，我们显示了两种主要相互作用。 首先，发现了阳离子-π 和 sigma-π 类型的分子间相互作用。 其次，THA+ 与 Trp86 残基一侧以及 Tyr337 残基另一侧之间建立了紧密的堆积相互作用。
