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A Novel Multi-Epitopic Peptide Vaccine Candidate Against Helicobacter pylori : In-Silico Identification, Design, Cloning and Validation Through Molecular Dynamics
International Journal of Peptide Research and Therapeutics ( IF 2.0 ) Pub Date : 2021-01-20 , DOI: 10.1007/s10989-020-10157-w
Pratik Ghosh 1 , Swarnav Bhakta 2 , Manojit Bhattacharya 3 , Ashish Ranjan Sharma 4 , Garima Sharma 5 , Sang-Soo Lee 4 , Chiranjib Chakraborty 2, 4
Affiliation  

Helicobacter pylori is a highly potential pathogen to colonize in the human stomach. This bacterial strain is now alarming serious health concern all over the world. Combating through available drugs is a difficult task due to lack of appropriate common targets against genetically diverse strains. Therefore, the developments of effective targets vaccines require alternative strategies to eliminate the H. pylori infection. In this study, we developed a novel vaccine construct using B-cell derived T-cell epitopes from four target antigenic proteins (HpaA, FlaA, FlaB and Omp18), and found the induction of possible immune response using advanced immunoinformatics approaches. In order to boost immune system, we tagged adjuvant (50S ribosomal protein L7/L12) with a suitable linker at the N-terminus side of vaccine sequence. Protein–protein docking between human Toll like receptor 5 (TLR5) and vaccine construct help to predict the way of inductive signaling that leads to immune-response. The calculated negative score (− 151.4, + / − 8.7) of molecular docking complex signify the best binding interface. Molecular dynamics simulation studies confirmed the proper docking between TLR5 and vaccine candidate. Moreover, Normal mode analysis (NMA) calculates the molecular motion of the docking complex. The low eigenvalue (2.935e−05) indicates the stable and flexible molecular motion in the binding interaction side. Finally, in-silico cloning of vaccine candidate was performed using expression vector pET28b (+) with the optimized restriction sites.



中文翻译:

一种针对幽门螺杆菌的新型多表位肽候选疫苗:通过分子动力学进行计算机识别、设计、克隆和验证

幽门螺杆菌是一种极有可能在人胃中定殖的病原体。这种细菌菌株现在正引起全世界的严重健康问题。由于缺乏针对遗传多样性菌株的适当共同目标,通过现有药物进行战斗是一项艰巨的任务。因此,有效靶标疫苗的开发需要替代策略来消除幽门螺杆菌感染。在这项研究中,我们使用来自四种靶抗原蛋白(HpaA、FlaA、FlaB 和 Omp18)的 B 细胞衍生的 T 细胞表位开发了一种新型疫苗构建体,并发现使用先进的免疫信息学方法诱导可能的免疫反应。为了增强免疫系统,我们在疫苗序列的 N 末端用合适的接头标记佐剂(50S 核糖体蛋白 L7/L12)。人类 Toll 样受体 5 (TLR5) 和疫苗构建体之间的蛋白质-蛋白质对接有助于预测导致免疫反应的诱导信号传导方式。计算出的分子对接复合物的负分 (- 151.4, + / - 8.7) 表示最佳结合界面。分子动力学模拟研究证实了 TLR5 和候选疫苗之间的正确对接。而且,正态模式分析 (NMA) 计算对接复合物的分子运动。低特征值(2.935e-05 ) 表示在结合相互作用侧的稳定和灵活的分子运动。最后,使用具有优化限制性位点的表达载体 pET28b (+) 对候选疫苗进行计算机克隆。

更新日期:2021-01-20
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