聚乙二醇修饰猪血红蛋白的计算机模拟研究

Study on Polyethylene Glycol Modified Porcine Hemoglobin Using Computer Modeling

对猪血红蛋白αβ二聚晶体结构的分析和氨基酸残基溶剂可及表面积的计算表明 ,猪血红蛋白表面赖氨酸 (Lys)上的氨基适合进行聚乙二醇 (PEG)修饰 ,对其修饰不会影响血红蛋白的携氧能力 ,在此基础上设计了连接物连接PEG和猪血红蛋白。猪血红蛋白和牛血红蛋白赖氨酸的保守性及其氨基可及性的差异表明 ,同源的蛋白质性质相似 ,但依据同源性分析单个氨基酸残基的性质时可能会有一定的偏差。分子模拟研究结果显示 。

The structure analysis of porcine hemoglobin αβ dimer and the calculation of solvent accessible surface of the amino acids showed the ε-amino groups of the lysine are suitable for modification by polyethylene glycol(PEG). The modification of the lysine residues will not affect the carring oxygen capacity of Hb. Three types of linker have been designed to connect PEG and porcine hemoglobin. The lysines between porcine and bovine hemoglobin (pHb and bHb) are highly conserved, but the solvent accessible surface of conserved lysines are different. These suggested that the properties of homologous proteins are similar in pHb and bHb, but the characteristic derived from the homology analysis will be deviated from the actual status. The results of molecular dynamics simulation suggested that the chemical modified porcine hemoglobin would be no immunogenicity.