新型冠状病毒相关蛋白DPP1的生物信息学分析及分子对接研究

Bioinformatic analysis and molecular docking studies of SARS-CoV-2 related protein DPP1

目的 利用生物信息学和分子对接方法分析预测新冠病毒相关蛋白二肽基肽酶1(Dipeptidyl peptidase 1,DPP1)的特征信息,为探究其作用机制和靶向药物的研发提供理论依据。方法 通过NCBI获得DPP1氨基酸序列,利用ProtParam、PredictProtein、PSORT、ProtScale、SignalP、TMHMM、SOMPA、PROSITE、SWISS-MODEL、SYBYL-X、STRING和IEBD等软件或服务器对其理化性质、亚细胞定位、信号肽、跨膜区、二、三级结构、活性中心、对接结合口袋、B/T细胞抗原表位及相互作用蛋白等进行预测分析。结果 DPP1由463个氨基酸残基构成,有1个信号肽序列,无跨膜区,是稳定的亲水性分泌蛋白。二级结构以无规卷曲为主,存在3个活性中心和2个功能结构域,涉及去除底物末端二肽的肽酶功能。三级结构模型显示其为四聚体结构,蛋白单体与小分子抑制剂的活性结合口袋由VAL40、LYS63、VAL65、THR67、VAL142、GLY143、THR144、ALA145、ASN148和THR150等核心氨基酸组成。DPP1主要与10个蛋白存在相互作用,具有10个B细胞抗原表位和14个T细胞抗原表位。结论 DPP1为含有信号肽序列的稳定亲水分泌蛋白,该蛋白含有B、T细胞抗原表位,该研究为DPP1在COVID-19重症化中的作用机制和开发抗新冠靶向药物奠定了基础。

Objective The characteristic information of SARS-CoV-2 related protein DPP1 was analyzed and predicted by bioinformatics and molecular docking method, providing theoretical basis for exploring its mechanism and developing targeted drugs. Methods According to the amino acid sequence of DPP1,the physical and chemical properties, subcellular localization, signal peptide, transmembrane region, secondary structure, active center, B cell and T cell epitopes and interacting protein were predicted and analyzed by ProtParam, PredictProtein, PSORT, ProtScale, SignalP, TMHMM, SOMPA, PROSITE, STRING、IEBD etc software or on-line servers. The tertiary structure of DPP1 was built by SWISS-MODEL. Active binding pockets of DPP1 were defined according to the docking results by SYBYL-X. Results Being composed of 463 amino acid residues, DPP1 was a stable hydrophilic secretory protein which had one signal peptide sequence, but no transmembrane region. Random coil was main secondary structure component. DPP1 contained 3 active centers and 2 functional domains which referred to the peptidase function by removing N-terminal dipeptide of substrate. The 3 active centers were belonged to the active site of sulfhydryl protease. The tertiary structure simulation showed that DPP1 was a tetramer. The docking results showed that the binding pockets were composed of 10 amino acids, which were described as VAL40,LYS63,VAL65,THR67,VAL142,GLY143,THR144,ALA145,ASN148 and THR150. Among them, LYS63 and THR144 were believed to play an important role in binding the small molecule inhibitors by the formation of hydrogen bond. DPP1 mainly interacted with 10 proteins. It was predicted that DPP1 had 10 B cell epitopes and 14 T cell epitopes. Conclusion DPP1 was a stable hydrophilic secretory protein with signal peptide sequence, and it had B and T cell epitopes. These results laid a foundation for further research on the mechanism of DPP1 in COVID-19 severity and the development of targeted drugs against COVID-19.