Background: Hepatitis B is a viral infection affecting the liver, causing severe damage. The disease affects 350-400 million people globally, with the highest rates in Asia, sub-Saharan Africa, and Central Asia. The materials used are the virus's protein, HBsAg, to be studied and to create a vaccine to treat the disease. The research aims to create a vaccine against hepatitis B using in vitro methods and applications like NCBI, MSA, modeler v10.5 program, and Swiss-model web server. Material and Methods: The sequence is obtained using UniProt, and the phylogenetic tree is visualized using MEGA11. The NetSurfP web server predicts secondary structures, and InterPro Scan aligns primary sequences with the homologous structure. Modeller v10.5 is used to predict and create a 3D model for the vaccine. Protein sequences are obtained using NCBI, Discovery Studio software, and VLP-based vaccines to predict the B and MHC I T cell epitope. The allergenicity and antigenicity of vaccines are tested using AlgPred web servers and VaxiJen v2.0. Homology modeling results are obtained and analyzed using the Ramachandran plot. Result: Salient points of this study dealing with the computational design of the Hepatitis B virus vaccine may be summarized as follows: different hepatitis B virus large envelope proteins were subjected to Multiple Sequence Alignment, and Phylogenetic Analysis identified the German sequence as the most recent strain. The secondary and tertiary structure of HBcAg core protein and HBsAg Germany HBV genotype D is predicted. Vaccine design was performed using a German HBsAg strain in BLAST, generating proteins from the selected sequences on Modeller v10.5 and refining the models through multiple templates. Predicted B and T cell epitopes from different web servers were combined into one peptide sequence of the designed vaccine. The allergenicity test using AlgPred forecasted the vaccine as a non-allergen, while VaxiJen demonstrated high antigenicity Conclusion: The Swiss-model web server generated a model for the final vaccine sequence. The Ramachandran plot analysis showed 84.7% of residues in the favored region, indicating a sound structural model. This high percentage of residues in the favored region suggests that the predicted 3D structure of the vaccine candidate is likely to be stable and biologically plausible. The Ramachandran plot is a good guide to the quality of the protein structures: the more residues that fall into the favored regions, the more reliable and generally the refinement of the models.

中文翻译：

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使用多重序列比对和 Modeller v10.5 进行 3D 蛋白质结构预测的乙型肝炎病毒疫苗的计算设计


背景：乙型肝炎是一种影响肝脏的病毒感染，会造成严重损害。该疾病影响全球 350-4 亿人，其中亚洲、撒哈拉以南非洲和中亚的发病率最高。使用的材料是病毒的蛋白质 HBsAg，有待研究并制造治疗该疾病的疫苗。该研究旨在使用 NCBI、MSA、modeler v10.5 程序和 Swiss-model Web 服务器等体外方法和应用程序创建针对乙型肝炎的疫苗。材料和方法：使用 UniProt 获得序列，并使用 MEGA11 可视化系统发育树。NetSurfP Web 服务器预测二级结构，InterPro Scan 将一级序列与同源结构对齐。Modeller v10.5 用于预测和创建疫苗的 3D 模型。使用 NCBI、Discovery Studio 软件和基于 VLP 的疫苗获得蛋白质序列，以预测 B 和 MHC I T 细胞表位。使用 AlgPred Web 服务器和 VaxiJen v2.0 测试疫苗的致敏性和抗原性。使用 Ramachandran 图获得和分析同源建模结果。结果：本研究涉及乙型肝炎病毒疫苗的计算设计，其要点可归纳为以下几点：对不同的乙型肝炎病毒大包膜蛋白进行多序列比对，系统发育分析确定德国序列为最新的毒株。预测 HBcAg 核心蛋白和 HBsAg 德国 HBV 基因型 D 的二级和三级结构。在 BLAST 中使用德国 HBsAg 菌株进行疫苗设计，从 Modeller v10.5 上的选定序列生成蛋白质，并通过多个模板优化模型。 将来自不同 Web 服务器的预测 B 细胞和 T 细胞表位组合成所设计疫苗的一个肽序列。使用 AlgPred 的致敏性测试预测疫苗为非过敏原，而 VaxiJen 表现出高抗原性结论：瑞士模型 Web 服务器为最终疫苗序列生成了一个模型。Ramachandran 图分析显示 84.7% 的残基位于有利区域，表明结构模型合理。青睐区域中如此高百分比的残基表明，候选疫苗的预测 3D 结构可能是稳定的且在生物学上是合理的。拉氏图是蛋白质结构质量的良好指南：落入受青睐区域的残基越多，模型就越可靠，通常越精细。