NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam.
School of Biotechnology, International University, Ho Chi Minh City, Vietnam.
J Mol Model. 2022 Feb 14;28(3):60. doi: 10.1007/s00894-022-05051-9.
For the purpose of discovering potential inhibitors of β-amyloid (BACE1), which is a crucial element in Alzheimer's disease (AD) pathogenesis, an in silico study of naturally occurring compounds was performed using precise computational approaches. Autodock4 package was preliminary used to predict the binding affinities to BACE1 of more than four thousand compounds presented in the Vietnamese plants (VIETHERB) database. Based on docking results, twenty top-lead compounds having the largest docking energy to BACE1 were rigorously examined using steered molecular dynamics (SMD) simulations. Interestingly, SMD results found that the binding affinity values of three compounds, including myricetin 3-O-(3''-galloylrhamnopyranoside), quercetin 3-O-neohesperidoside, and hydroxysafflor yellow A, are remarkably higher than that of the well-known BACE1 inhibitor, 23I, and these compounds can thus be considered the promising candidates for inhibitors of BACE1.
为了发现β-淀粉样蛋白（BACE1）的潜在抑制剂，该蛋白是阿尔茨海默病（AD）发病机制中的关键因素，使用精确的计算方法对天然存在的化合物进行了计算机研究。使用 Autodock4 包初步预测了越南植物（VIETHERB）数据库中四千多种化合物与 BACE1 的结合亲和力。根据对接结果，使用定向分子动力学（SMD）模拟对与 BACE1 结合能最大的前 20 个先导化合物进行了严格检查。有趣的是，SMD 结果发现，三种化合物（包括杨梅素 3-O-(3''-没食子酰基鼠李吡喃糖苷)、槲皮素 3-O-新橙皮糖苷和羟基红花黄色素 A）的结合亲和力值明显高于著名的 BACE1 抑制剂 23I，因此这些化合物可以被认为是 BACE1 抑制剂的有前途的候选物。
