A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors
A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors
复制标题
诱导拟合对接新方法（GENIUS）及其在新型HCV NS3-4A蛋白酶抑制剂虚拟筛选中的应用
DOI：
10.1016/j.bmc.2011.09.023
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发表时间：
2011
影响因子：
3.5
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Takaya D;Sakamoto N;et al.
丙型肝炎病毒 (HCV) 是慢性肝病的病原体，全世界约有 1.7 亿人感染该病毒。 HCV NS3-4A 丝氨酸蛋白酶对该病毒的复制至关重要，因此已被作为抗 HCV 药物的有吸引力的靶标进行研究。在这项研究中，我们开发了新的诱导拟合对接程序（天才），并将其应用于发现一类新的 NS3-4A 蛋白酶抑制剂（IC50=1–10μM，包括高选择性指数）。基于对接模型，对由此鉴定出的新抑制剂进行了修改，并揭示了初步的结构-活性关系。此外，通过使用富集因子验证了计算机筛选性能的天才。我们相信我们设计的支架可以有助于改善 HCV 化疗。
Hepatitis C virus (HCV) is an etiologic agent of chronic liver disease, and approximately 170 million people worldwide are infected with the virus. HCV NS3-4A serine protease is essential for the replication of this virus, and thus has been investigated as an attractive target for anti-HCV drugs. In this study, we developed our new induced-fit docking program (genius), and applied it to the discovery of a new class of NS3-4A protease inhibitors (IC50=1–10μM including high selectivity index). The new inhibitors thus identified were modified, based on the docking models, and revealed preliminary structure–activity relationships. Moreover, the genius in silico screening performance was validated by using an enrichment factor. We believe our designed scaffold could contribute to the improvement of HCV chemotherapy.