不同血清型腺相关病毒衣壳蛋白氨基酸残基序列分析

Sequence analysis of amino acid residues in adeno-associated virus capsid protein of different serotypes

目的:分析不同血清型腺相关病毒衣壳蛋白(VP1)氨基酸残基序列,建立相似性比较方法和数据库,预测VP1氨基酸残基序列突变后可能隶属的血清型。方法:对不同血清型腺相关病毒VP1氨基酸残基序列分析,找出共同序列,并对序列进行对齐。分别对疏水氨基酸残基、亲水氨基酸残基和酸/碱氨基酸残基进行单独赋值,赋值参数包括侧链长度、基团数量和解离/结合强度等,再用相关系数法和差值法计算相似度。规定全局电荷决定界值,判断电荷的变化是否会引起蛋白质周围电场的显著变化。最后综合考虑四者的关系,给出与已知血清型VP1氨基酸残基序相似度。通过其他已知血清型的VP1氨基酸残基序进行验证。结果:基本上可以区分不同的血清型,并且对相同血清型中的不同亚型具有一定的容忍度。结论:对腺相关病毒衣壳蛋白VP1氨基酸残基序列与其血清型间的联系进行了探讨,希望对重组腺相关病毒为载体的基因治疗研发提供支持。

Objective:To analyze the amino acid residue sequences of adeno-associated virus capsid protein(VP1)of different serotypes,and establish the similarity comparison method and database,and to predict the serotypes that VP1 may belong to after amino acid residue sequence mutation.Methods:The amino acid residues of VP1 of adeno-associated virus of different serotypes were analyzed to find out a common sequence,and the sequences were aligned.The hydrophobic amino acid residues,hydrophilic amino acid residues and acid/base amino acid residues were assigned separately.The assignment parameters included side chain length,group number and dissociation/binding strength.Then the similarity was calculated by correlation coefficient method and difference method.The global charge was defined to determine the boundary value,and determine whether the change of charge will cause a significant change in the electric field around the protein.Finally,considering the relationship of the four,the similarity with the known serological sequences was given.The protein amino acid sequences of other known serotypes were verified.Results:Basically,different serotypes could be distinguished,and different subtypes of the same serotype have a certain tolerance.Conclusion:The relationship between the amino acid residues sequence of adeno-associated VP1 and its serotype was discussed,hoping to provide support for the research and development of recombinant adeno-associated virus as a vector for gene therapy.