连接聚酰胺对DNA序列识别的理论极限
The theoretical limits of DNA sequence discrimination by linked polyamides.
作者信息
Walker W L, Landaw E M, Dickerson R E, Goodsell D S
机构信息
Department of Biomathematics and the Molecular Biology Institute, University of California, Los Angeles, CA 90024, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4315-20. doi: 10.1073/pnas.95.8.4315.
Linked polyamides bind in the minor groove of double-stranded DNA in a partially sequence-specific manner. This report analyzes the theoretical limits of DNA sequence discrimination by linked polyamides composed of two to four different types of heterocyclic rings, determining (i) the optimal choice of base-binding specificity for each ring and (ii) the optimal design for a polyamide composed of these rings to target a given DNA sequence and designed to maximize the fraction of the total polyamide binding to the specified target sequence relative to all other sequences. The results show that, fortuitously, polyamides composed of pyrrole, a naturally occurring G-excluding element, and imidazole, a rationally designed G-favoring element, have features similar to the theoretical optimum design for polyamides composed of two different rings. The results also show that, in polyamides composed of two or three types of heterocyclic rings, choosing a nonspecific "placeholder" ring, which binds equally strongly to each of the four bases, along with one or two base-specific rings will often enhance sequence specificity over a polyamide composed entirely of base-specific rings.
连接的聚酰胺以部分序列特异性的方式结合于双链DNA的小沟中。本报告分析了由两到四种不同类型杂环组成的连接聚酰胺对DNA序列识别的理论极限，确定了（i）每个环的碱基结合特异性的最佳选择，以及（ii）由这些环组成的聚酰胺针对给定DNA序列的最佳设计，该设计旨在使与指定靶序列结合的总聚酰胺相对于所有其他序列的比例最大化。结果表明，幸运的是，由天然存在的排除鸟嘌呤的元件吡咯和合理设计的偏好鸟嘌呤的元件咪唑组成的聚酰胺，具有与由两种不同环组成的聚酰胺的理论最佳设计相似的特征。结果还表明，在由两种或三种杂环组成的聚酰胺中，选择一个对四种碱基结合强度相同的非特异性“占位”环，与一个或两个碱基特异性环一起，通常会比完全由碱基特异性环组成的聚酰胺增强序列特异性。
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