基于云南臭蛙抗菌肽序列分析的药物设计策略

摘要

通过生物信息学手段分析云南臭蛙抗菌肽的结构与功能,为合成此类抗菌肤和通过基因工程方法生产新药物提供理论依据.通过互联网和计算机软件比较和分析了云南臭蛙抗菌肽的成熟肤序列和二级结构,设计了一个具有抗菌活性的抗菌肽分子.结果表明:成熟肽的正电荷和α螺旋结构与抗菌肽的活性密切相关.根据分析结果,设计了一条抗菌肽序列:GL(A/V/I) AANFLPK (T) AF (L) CXXXK (R) KC,此抗菌肽分子可能具有较强的抗菌活性.表明正电荷是影响抗菌肤与致病菌细胞膜结合的关键,而α螺旋的两亲性结构则在抗菌肽插入脂质双分子层中起重要作用.在维持保守氨基酸不变的情况下,可在适当位置改变或置换一些氨基酸,对天然抗菌肽进行基因改造或人工合成此类抗菌肤,不失为开发新药物的一条捷径.%In order to design a new type of antimicrobial peptides and provide theoretical basis for the new drug development using synthesis and genetic engineering methods, the structure and function of the antibacterial peptide from Rana andersonii are analyzed. The analysis is implemented online or computing with software, the sequence characters and secondary structure of the mature peptide of the antibacterial peptide from Rana andersonii are analyzed. A new antimicrobial peptides sequence having strong activity is designed based on the analysis. The analysis data shows that the positive charge and the spatial structure of the alpha helix may be closely correlated to the activity of the antibacterial peptide. A new antimicrobial peptides sequence, GL(A/V/I) AANFLPK(T) AFCL)CXXXK(R) KC, is designed, and succedent analysis shows it may present strong antimicrobial activity. The positive charge is a crucial factor for antibacterial peptides combined with pathogenic bacteria, and the alpha helix structure plays an important role in the antimicrobial peptides inserting into the membrane of pathogens. In the case of maintaining the conservative amino acids, some amino acids in the appropriate location of natural antimicrobial peptides can be changed or replaced and peptide which artificially synthesized become possibly. From the results above, development of new drugs could be a shortcut by genetic modification of natural peptides or artificially synthesized.