分子模拟指导核酸适配体文库设计

The Design of Aptamer Candidate Pool Guided by Molecular Simulation

核酸适配体是利用配体指数富集的系统进化技术(SELEX)从随机文库中筛选获得一段有功能的单链寡核苷酸。但因筛选过程中的文库选择、洗涤次数、分离效率、缓冲液离子含量和pH值等多种因素的影响,迄今所报道的亲和力与特异性都很高的核酸适配体为数不多。初始文库是核酸适配体筛选的源头,作为SELEX技术的根本,其设计是否合理直接影响到筛选的成败和效率。分子模拟能以核酸适配体文库为主体,计算机为主要工具,发展多种结构模拟与分析工具,辅助核酸适配体文库的合理设计。本文综述了现阶段利用分子模拟进行核酸适配体初始文库设计的相关方法,希望能为从源头上提高核酸适配体筛选的成功率提供线索。

Aptamers are functional single-stranded oligonucleotides selected from random libraries by SELEX(systematic evolution of ligands by exponential enrichment). However, the number of reported aptamers with high affinity and specificity so far is still less than satisfactory because of library selection, washing times, separation efficiency, ion, pH value of buffer and so on. As the fundamental of SELEX process, the initial library is the primary source for screening SELEX. Properly design of initial library is directly related to the outcome and efficiency of the selection. A variety of structural simulation can be generated for aptamer library and relevant analysis tools can be developed by molecular simulation. This paper summaries the present methods of using molecular simulation to guide the design of aptamer initial library, hoping to provide clues for improving the success rate of aptamer screening from the initial source.