Alzheimer’s disease (AD) is a growing global health concern that affects 10% of the population aged above 65 years. A growing body of evidence indicates that multi-targeted drugs might be useful therapeutic options owing to the heterogeneity of AD pathology. The current study exploited advanced computational biology tools to identify ligands that might display effective binding to two protein targets in the context of AD. The present study used in silico virtual screening of small molecules library to identify effectiveness against two AD targets viz. acetyl cholinesterase (AChE) and glycogen synthase kinase-3β (GSK-3β). PyRX-Python prescription with AutodockVina was used to generate binding energy profiles. Further screening was accomplished using SwissADME and molecular interaction studies. The present study obtained 48 ligands (absolute binding energy >8 kcal/mol), by virtual screening of 100 ligands. Among those, 13 ligands (BRW, 6VK, 6Z5, SMH, X37, 55E, 65 A, IQ6, 6VL, 6VM, F1B, 6Z2 and GVP) were selected based on blood brain barrier (BBB) permeability, acceptable ADME properties as well as their molecular interaction profiles with the aforementioned AD-targets. The present study has predicted certain molecules that appear worthy to be tested for effectiveness against two AD targets, namely AChE and GSK-3β. However, the results warrant further wet laboratory validation, as computational studies are merely predictive in nature. This approach might be useful for future treatment of AD.

Communicated by Ramaswamy H. Sarma

阿尔茨海默氏病（AD）是一种日益严重的全球性健康问题，影响了65岁以上人口的10％。越来越多的证据表明，由于AD病理学的异质性，多靶点药物可能是有用的治疗选择。当前的研究利用先进的计算生物学工具来鉴定在AD情况下​​可能显示与两个蛋白质靶标有效结合的配体。本研究已用于计算机虚拟筛选小分子文库，以鉴定针对两个AD目标的功效，即。乙酰胆碱酯酶（AChE）和糖原合酶激酶3β（GSK-3β）。使用具有AutodockVina的PyRX-Python处方生成结合能分布图。使用SwissADME和分子相互作用研究完成了进一步的筛选。通过虚拟筛选100个配体，本研究获得了48个配体（绝对结合能> 8 kcal / mol）。其中，根据血脑屏障（BBB）的渗透性，可接受的ADME特性，还选择了13个配体（BRW，6VK，6Z5，SMH，X37、55E，65 A，IQ6、6VL，6VM，F1B，6Z2和GVP）作为它们与上述AD-靶标的分子相互作用图。本研究预测某些分子似乎值得针对两个AD靶进行测试，即AChE和GSK-3β。但是，由于计算研究本质上仅是预测性的，因此结果值得进一步进行湿法实验室验证。这种方法可能对将来的AD治疗有用。

由Ramaswamy H.Sarma沟通