Identification of Potential Leptospira Phosphoheptose Isomerase Inhibitors Through Virtual High-Throughput Screening

作     者：Amineni Umamaheswari Dibyabhaba Pradhan Marisetty Hemanthkumar 

作者机构：SVIMS Bioinformatics Centre SVIMS University Agricultural Research Station Perumallapalle 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2010年第8卷第4期

页      面：246-255页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Department of Biotechnology  Ministry of Science and Technology  India  DBT 

主　　题：LPS biosynthesis Leptospira homology modeling virtual high-throughput screening GmhA inhibitors 

摘      要：The life-threatening infections caused by Leptospira serovars demand the need for designing anti-leptospirosis drugs. The present study encompasses exploring inhibitors against phosphoheptose isomerase （GmhA） of Leptospira, which is vital for lipopolysaccharide （LPS） biosynthesis and is identified as a common drug target through the subtractive genomic approach. GmhA model was built in Modeller 9v7. Structural refinement and energy minimization of the predicted model was carried out using Maestro 9.0. The refined model reliability was assessed through Procheck, ProSA, ProQ and Profile 3D. The substrate-based virtual high-throughput screening （VHTS） in *** Meta-Database tool generated an in-house library of 354 substrate structural analogs. Furthermore, structure-based VHTS from the in-house library with different conformations of each ligand provided 14 novel competitive inhibitors. The model together with insight gained from the VHTS would be a promising starting point for developing anti-leptospirosis competitive inhibitors targeting LPS biosynthesis pathway.