用于鉴定人SMO受体高亲和力抑制剂的分子对接方法

Molecular docking approaches in identification of High affinity inhibitors of Human SMO receptor.

作者信息

Akare Uday Raj, Bandaru Srinivas, Shaheen Uzma, Singh Pramod Kumar, Tiwari Geet, Singare Paramanand, Nayarisseri Anuraj, Banerjee Tushar

机构信息

Bioinformatics Research Laboratory, Eminent Biosciences, Vijaynagar, Indore - 452010, Madhya Pradesh, India.

Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad - 500 016, Telangana, India.

出版信息

Bioinformation. 2014 Dec 31;10(12):737-42. doi: 10.6026/97320630010737. eCollection 2014.

Inappropriate activation of the Hh signaling pathway has been implicated in the development of several types of cancers including prostate, lung, pancreas, breast, brain and skin. Present study identified the binding affinities of eight established inhibitors viz., Cyclopamine, Saridegib, Itraconazole, LDE-225, TAK-441, BMS-833923 (XL139), PF-04449913 and Vismodegib targeting SMO receptor - a candidate protein involved in hedgehog pathway and sought to identify the best amongst the established inhibitors through by molecular docking. Exelxis® BMS 833923 (XL 139) demonstrated superior binding affinity aided by MolDock scoring docking algorithm. Further BMS 833923 (XL 139) was evaluated for pharmacophoric features which revealed appreciable ligand receptor interactions.

Hh信号通路的不适当激活与包括前列腺癌、肺癌、胰腺癌、乳腺癌、脑癌和皮肤癌在内的多种癌症的发生有关。本研究确定了八种已确立的抑制剂，即环杷明、沙立度胺、伊曲康唑、LDE-225、TAK-441、BMS-833923（XL139）、PF-04449913和维莫德吉针对SMO受体的结合亲和力，SMO受体是一种参与刺猬信号通路的候选蛋白，并试图通过分子对接在已确立的抑制剂中找出最佳抑制剂。借助MolDock评分对接算法，Exelxis® BMS 833923（XL 139）表现出卓越的结合亲和力。此外，对BMS 833923（XL 139）的药效团特征进行了评估，结果显示其配体与受体之间存在明显的相互作用。