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目的:虚拟筛选具有组蛋白去乙酰化酶(HDAC)抑制作用的木脂素类化合物。方法:以“木酯素”“Lignanoid”为关键词,查询中国知网、维普、Pub Med等中外文数据库中相关文献,收集木脂素类化合物作为配体构建配体库,从蛋白质晶体数据库(PDB)中选取两个HDAC受体HDAC2(PDB code:4LXZ)和HDAC8(PDB code:1T69),运用SYBYL-X 2.0软件将配体和受体三维结构的活性位点进行对接,用总得分来反映配体与受体的亲和力大小。结果:将收集的345个木质素类化合物与4LXZ、1T69原配体一起构建了有347种配体的配体库,其中编号为275、271、110、200、056、258、181、129、037、270、187的配体与HDAC2和HDAC8受体有较好的亲和力,配体与受体的残基以氢键的方式结合。结论:木脂素类化合物具有抑制HDAC的作用;虚拟筛选方法可作为预测天然产物潜在活性的有效手段,为木脂素类化合物新的药理活性研究提供了快捷途径和理论指导。
Objective: To screen the lignans with histone deacetylase (HDAC) suppressive effect. METHODS: With the key words “lignanoid” and “Lignanoid”, the related literatures in Chinese and English databases such as CNKI, VIP and Pub Med were searched and lignans were collected as ligands to construct the ligand library. Two HDAC receptors HDAC2 (PDB code: 4LXZ) and HDAC8 (PDB code: 1T69) were selected from the protein crystal database (PDB). The SYBYL-X 2.0 software was used to dock the active sites of the three- , With the total score to reflect the affinity of ligand and receptor size. Results: The collected 345 lignin compounds were combined with 4LXZ and 1T69 primary ligands to construct a pool of 347 ligands, including 275,271,110,200,056,258,181,129, The ligands 037, 270, and 187 have good affinity with the HDAC2 and HDAC8 receptors, and the ligand and receptor residues are hydrogen-bonded. CONCLUSION: Lignans can inhibit HDAC. The virtual screening method can be used as an effective method to predict the potential activity of natural products, which provides a quick way and theoretical guidance for the new pharmacological activities of lignans.