BACE-1靶向小分子抑制剂虚拟筛选

Discovery BACE-1 inhibitors from various databases based on virtual screening method

β-secretase分泌酶(BACE-1)是一种天冬氨酸蛋白酶,BACE-1是控制脑内淀粉样前体蛋白水解产生β-淀粉样蛋白的关键酶,其抑制剂将是控制阿尔茨海默病的一个有效途径。本研究首先根据Lipinski类药性评价规则对天然产物数据库、中药数据库以及FDA药品数据库中的化合物进行类药性筛选,然后采用分子对接的方法从类药性良好的化合物中筛选与BACE-1对接分数较高的化合物。通过ADME预测,筛选得到的7个化合物具有较好的成药性。研究分子对接下的互作模式以及通过自由结合能验证复合物体系的稳定性,最终得到4个潜在的BACE-1靶向小分子抑制剂。本研究为BACE-1抑制剂的开发提供了设计思路,筛选得到的化合物有望成为阿尔茨海默病的有效治疗药物。

β-Secretase(BACE-1)is a winter amino acid protease, which is a key enzyme that controls the hydrolysis of amyloid precursor proteins in the brain to produce β-amyloid proteins, and its inhibitors will be an effective way to control Alzheimer′s disease.This study first screened compounds in natural product database, Chinese medicine database and FDA drug database according to Lippinski drug properties evaluation rules, and then used molecular docking method to screen compounds with higher butt scores with BACE-1 from drug-like compounds.Through ADME prediction, the seven compounds selected had good medicinal quality.Then the stability of the complex system could be verified by the interaction mode and free binding under molecular docking, and finally four potential BACE-1 targeting small molecule inhibitors were obtained.This study provided a design idea for the development of BACE-1 inhibitors, and the selected compounds were expected to become effective treatment drugs for Alzheimer′s disease.