Alom Md Murshid, Bonna Rejwana Parvin, Islam Ariful, Alom Md Wasim, Rahman Md Ekhtiar, Faruqe Md Omar, Khalekuzzaman Md, Zaman Rashed, Islam Md Asadul
Professor O.I Joarder DNA and Chromosome Research Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
Int J Alzheimers Dis. 2023 Sep 15;2023:8877757. doi: 10.1155/2023/8877757. eCollection 2023.
Alzheimer's disease (AD) is a serious threat to the global health care system and is brought on by a series of factors that cause neuronal dysfunction and impairment in memory and cognitive decline. This study investigated the therapeutic potential of phytochemicals that belong to the ten regularly used spice plants, based on their binding affinity with AD-associated proteins. Comprehensive docking studies were performed using AutoDock Vina in PyRx followed by molecular dynamic (MD) simulations using AMBER 14. The docking study of the chosen molecules revealed the binding energies of their interactions with the target proteins, while MD simulations were carried out to verify the steadiness of bound complexes. Through the Lipinski filter and admetSAR analysis, the chosen compounds' pharmacokinetic characteristics and drug likeness were also examined. The pharmacophore mapping study was also done and analyzed for best selected molecules. Additionally, principal component analysis (PCA) was used to examine how the general motion of the protein changed. The results showed quercetin and myricetin to be potential inhibitors of AChE and alpha-amyrin and beta-chlorogenin to be potential inhibitors of BuChE, exhibiting best binding energies comparable to those of donepezil, used as a positive control. The multiple descriptors from the simulation study, root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bond, radius of gyration (Rg), and solvent-accessible surface areas (SASA), confirm the stable nature of the protein-ligand complexes. Molecular mechanic Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations indicated the energetically favorable binding of the ligands to the protein. Finally, according to pharmacokinetic properties and drug likeness, characteristics showed that quercetin and myricetin for AChE and alpha-amyrin and beta-chlorogenin for BuChE were found to be the most effective agents for treating the AD.
阿尔茨海默病（AD）是全球医疗保健系统面临的严重威胁，它由一系列导致神经元功能障碍、记忆受损和认知衰退的因素引发。本研究基于十种常用香料植物中的植物化学物质与AD相关蛋白的结合亲和力，探究了它们的治疗潜力。使用PyRx中的AutoDock Vina进行了全面的对接研究，随后使用AMBER 14进行分子动力学（MD）模拟。所选分子的对接研究揭示了它们与靶蛋白相互作用的结合能，同时进行MD模拟以验证结合复合物的稳定性。通过Lipinski筛选和admetSAR分析，还考察了所选化合物的药代动力学特征和药物相似性。还进行了药效团映射研究并对最佳选择的分子进行了分析。此外，主成分分析（PCA）用于检查蛋白质的整体运动如何变化。结果表明，槲皮素和杨梅素是乙酰胆碱酯酶（AChE）的潜在抑制剂，α-香树精和β-绿原酸是丁酰胆碱酯酶（BuChE）的潜在抑制剂，它们表现出与用作阳性对照的多奈哌齐相当的最佳结合能。模拟研究中的多个描述符，均方根偏差（RMSD）、均方根波动（RMSF）、氢键、回转半径（Rg）和溶剂可及表面积（SASA），证实了蛋白质-配体复合物的稳定性质。分子力学泊松-玻尔兹曼表面积（MM-PBSA）结合自由能计算表明配体与蛋白质的结合在能量上是有利的。最后，根据药代动力学性质和药物相似性特征，发现用于治疗AChE的槲皮素和杨梅素以及用于治疗BuChE的α-香树精和β-绿原酸是治疗AD最有效的药物。
