虚拟筛选和分子动力学模拟研究:筛选弗林蛋白酶的潜在抑制剂

Virtual screening and molecular dynamics simulation studies to identify potential inhibitors of Furin

通过分子对接和分子动力学模拟的方法,进行基于弗林蛋白(Furin)受体的虚拟筛选,以寻找Furin的潜在抑制剂。利用Sybyl软件构建基于Furin受体的药效团模型,在ZINC数据库中筛选出符合药效团模型的小分子,将小分子与Furin蛋白进行分子对接,最终筛选出4个符合条件的小分子。对4个复合物进行100 ns分子动力学模拟,并对轨迹进行RMSD和RMSF分析。通过分子力学-广义Born表面积法(MMGBSA)分析Furin受体和小分子配体平衡后的结合能,对比发现ZINC7664的结合能最低。所以小分子ZINC7664与Furin受体的结合最稳定,具有较好的应用前景,可用于设计有效的抑制Furin的药物。

In this study, virtual screening based on Furin receptor was carried out by means of molecular docking and molecular dynamics simulations to find potential inhibitors of Furin. The pharmacophore model based on Furin receptor was constructed by Sybyl. Drug molecules were screened from ZINC database according to the pharmacophore model. The screened drug molecules were docked with Furin protein. Finally, four qualified drug molecules were screened. The four complexes were calculated by molecular dynamics simulations for 100 ns. RMSD and RMSF were calculated. The binding energies of Furin receptors with drug molecular ligands were analyzed by MMGBSA. It was found that the binding energy of Furin-ZINC7664 was the lowest one, which indicated that the drug molecule ZINC7664 is the most stable potential inhibitor to Furin and could be used to design the effective anti-Furin drugs.