Samal Himanshu Bhusan, Prava Jyoti, Suar Mrutyunjay, Mahapatra Rajani Kanta
School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
J Theor Biol. 2015 Mar 21;369:67-79. doi: 10.1016/j.jtbi.2015.01.022. Epub 2015 Jan 28.
A computational, comparative genomics workflow was defined for the identification of novel therapeutic candidates against Salmonella Typhimurium LT2, with the aim that the selected targets should be essential to the pathogen, and have no homology with the human host. Bioinformatics analysis identified 43 proteins as non-host essential, which could serve as potential drug and vaccine targets. Additional prioritization parameters characterized 13 proteins as vaccine candidates while druggability of each of the identified proteins was evaluated by the Drug Bank database prioritized same number proteins suitable for drug targets. As a case study we built a homology model of one of the potential drug targets MurD ligase using MODELLER (9v12) software. The model has been further explored for in silico docking study with the inhibitors having druggability potential from the Drug Bank database. Results from this study could facilitate selective S. Typhimurium LT2 proteins for drug design and vaccine production pipelines.
定义了一种计算比较基因组学工作流程，用于鉴定针对鼠伤寒沙门氏菌LT2的新型治疗候选物，目标是所选靶点对病原体至关重要，且与人类宿主无同源性。生物信息学分析确定了43种非宿主必需蛋白，它们可作为潜在的药物和疫苗靶点。额外的优先级参数将13种蛋白表征为疫苗候选物，同时通过药物银行数据库评估每种已鉴定蛋白的可成药性，优先选择了相同数量适合作为药物靶点的蛋白。作为案例研究，我们使用MODELLER（9v12）软件构建了一种潜在药物靶点MurD连接酶的同源模型。该模型已进一步用于与药物银行数据库中具有潜在可成药性的抑制剂进行计算机对接研究。本研究结果有助于为药物设计和疫苗生产流程选择鼠伤寒沙门氏菌LT2的特定蛋白。
