使用遗传算法优化登革热病毒信封蛋白的肽抑制剂

Optimization of peptide inhibitors targeting E protein of dengue virus using genetic algorithms

登革热病毒严重威胁了人类的健康.目前仍无有效的治疗措施.膜融合是登革热病毒入侵细胞的第一步.信封蛋白的构象变化在膜融合过程中起到关键作用.研发针对信封蛋白的肽抑制剂为治疗登革热提供了潜在的重要靶点.设计了优化针对信封蛋白的肽抑制剂的遗传算法,分别使用3种不同的选择算子(轮盘法、锦标赛法和并行法),对初始父代进行300代的优化.通过比较发现并行法的结果较好,命名最优的结果为DN58ga.与此同时还获得了一些多肽衍生物.通过计算验证,这些多肽比父代表现出与登革热病毒信封蛋白更好的结合能力.这些新的肽抑制剂有可能打断融合过程中的蛋白-蛋白相互作用,并有望作为开发登革热病毒信封蛋白新型抑制剂的起点.

Dengue virus is a serious threat to human health,but there is no effective treatment.Membrane fusion is the first step of viral infection.The conformational changes of envelope(E)protein play a key role in the process of membrane fusion.Therefore,the development of peptide inhibitors targeting E protein provides new ideas for the treatment of dengue fever.In our study,a genetic algorithm for optimizing DN58opt,which is an effective inhibitor targeting E protein of dengue virus peptide was designed.Three different selection operators:roulette method,championship method and parallel method were used to optimize DN58opt for 300 generations.The results of parallel method were better than other method,and DN58ga was obtained.At the same time,some polypeptide derivatives were received.Through computer evaluation,these polypeptides showed better binding affinities than DN58opt.The novel peptide inhibitors have potential to disrupt the protein-protein interaction in the fusion process and may serve as starting points for development of novel inhibitors for viral E proteins of dengue virus.