PDF(Pubmed)
Abstract：
UNASSIGNED: Trypanosoma cruzi is a protozoan parasite that causes the tropical ailment known as Chagas disease, which has its origins in South America. Globally, it has a major impact on health and is transported by insect vector that serves as a parasite. Given the scarcity of vaccines and the limited treatment choices, we conducted a comprehensive investigation of core proteomics to explore a potential reverse vaccine candidate with high antigenicity.
UNASSIGNED: To identify the immunodominant epitopes, T. cruzi core proteomics was initially explored. Consequently, the vaccine sequence was engineered to possess characteristics of non-allergenicity, antigenicity, immunogenicity, and enhanced solubility. After modeling the tertiary structure of the human TLR4 receptor, the binding affinities were assessed employing molecular docking and molecular dynamics simulations (MDS).
UNASSIGNED: Docking of the final vaccine design with TLR4 receptors revealed substantial hydrogen bond interactions. A server-based methodology for immunological simulation was developed to forecast the effectiveness against antibodies (IgM + IgG) and interferons (IFN-g). The MDS analysis revealed notable levels of structural compactness and binding stability with average RMSD of 5.03 Aring;, beta-factor 1.09e+5 Å, Rg is 44.7 Aring; and RMSF of 49.50 Aring;. This is followed by binding free energies calculation. The system stability was compromised by the complexes, as evidenced by their corresponding Gibbs free energies of -54.6 kcal/mol.
UNASSIGNED: Subtractive proteomics approach was applied to determine the antigenic regions of the T cruzi. Our study utilized computational techniques to identify B- and T-cell epitopes in the T. cruzi core proteome. In current study the developed vaccine candidate exhibits immunodominant features. Our findings suggest that formulating a vaccine targeting the causative agent of Chagas disease should be the initial step in its development.
UNASSIGNED: To identify the immunodominant epitopes, T. cruzi core proteomics was initially explored. Consequently, the vaccine sequence was engineered to possess characteristics of non-allergenicity, antigenicity, immunogenicity, and enhanced solubility. After modeling the tertiary structure of the human TLR4 receptor, the binding affinities were assessed employing molecular docking and molecular dynamics simulations (MDS).
UNASSIGNED: Docking of the final vaccine design with TLR4 receptors revealed substantial hydrogen bond interactions. A server-based methodology for immunological simulation was developed to forecast the effectiveness against antibodies (IgM + IgG) and interferons (IFN-g). The MDS analysis revealed notable levels of structural compactness and binding stability with average RMSD of 5.03 Aring;, beta-factor 1.09e+5 Å, Rg is 44.7 Aring; and RMSF of 49.50 Aring;. This is followed by binding free energies calculation. The system stability was compromised by the complexes, as evidenced by their corresponding Gibbs free energies of -54.6 kcal/mol.
UNASSIGNED: Subtractive proteomics approach was applied to determine the antigenic regions of the T cruzi. Our study utilized computational techniques to identify B- and T-cell epitopes in the T. cruzi core proteome. In current study the developed vaccine candidate exhibits immunodominant features. Our findings suggest that formulating a vaccine targeting the causative agent of Chagas disease should be the initial step in its development.
摘要：
■克氏锥虫是一种原生动物寄生虫，可引起称为恰加斯病的热带疾病，它起源于南美。全球范围内,它对健康有重大影响，并由作为寄生虫的昆虫媒介运输。鉴于疫苗的稀缺性和有限的治疗选择，我们对核心蛋白质组学进行了全面研究，以探索具有高抗原性的潜在反向候选疫苗。
■为了鉴定免疫显性表位，最初探索了T.cruzi核心蛋白质组学。因此,疫苗序列被设计成具有非变应原性的特征，抗原性,免疫原性,和增强的溶解度。在对人类TLR4受体的三级结构进行建模后，使用分子对接和分子动力学模拟(MDS)评估结合亲和力。
■最终疫苗设计与TLR4受体的对接揭示了大量的氢键相互作用。开发了一种基于服务器的免疫学模拟方法，以预测抗抗体（IgMIgG）和干扰素（IFN-g）的有效性。MDS分析显示结构致密性和结合稳定性显著，平均RMSD为5.03Aming；β系数1.09e+5,Rg为44.7阿林；RMSF为49.50阿林；。接下来是结合自由能计算。复合物损害了系统的稳定性，其相应的吉布斯自由能为-54.6kcal/mol。
■应用减法蛋白质组学方法来确定克氏T的抗原区域。我们的研究利用计算技术来鉴定克氏锥虫核心蛋白质组中的B细胞和T细胞表位。在目前的研究中,开发的候选疫苗表现出免疫显性特征。我们的发现表明，针对恰加斯病的病原体制定疫苗应该是其开发的第一步。
■为了鉴定免疫显性表位，最初探索了T.cruzi核心蛋白质组学。因此,疫苗序列被设计成具有非变应原性的特征，抗原性,免疫原性,和增强的溶解度。在对人类TLR4受体的三级结构进行建模后，使用分子对接和分子动力学模拟(MDS)评估结合亲和力。
■最终疫苗设计与TLR4受体的对接揭示了大量的氢键相互作用。开发了一种基于服务器的免疫学模拟方法，以预测抗抗体（IgMIgG）和干扰素（IFN-g）的有效性。MDS分析显示结构致密性和结合稳定性显著，平均RMSD为5.03Aming；β系数1.09e+5,Rg为44.7阿林；RMSF为49.50阿林；。接下来是结合自由能计算。复合物损害了系统的稳定性，其相应的吉布斯自由能为-54.6kcal/mol。
■应用减法蛋白质组学方法来确定克氏T的抗原区域。我们的研究利用计算技术来鉴定克氏锥虫核心蛋白质组中的B细胞和T细胞表位。在目前的研究中,开发的候选疫苗表现出免疫显性特征。我们的发现表明，针对恰加斯病的病原体制定疫苗应该是其开发的第一步。
