Estimation of the DNA sequence discriminatory ability of hairpin-linked lexitropsins.
Estimation of the DNA sequence discriminatory ability of hairpin-linked lexitropsins.
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发夹连接的舒张蛋白的 DNA 序列辨别能力的估计。
DOI：
10.1073/pnas.94.11.5634
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发表时间：
1997
影响因子：
11.1
通讯作者：
Goodsell,DS
中科院分区：
文献类型：
--
作者：
Walker,WL;Landaw,EM;Dickerson,RE;Goodsell,DS
含有n-甲基咪唑和n-甲基吡咯的三环和四环聚酰胺，以及它们的发夹连接衍生物，以序列特异性的方式在DNA的小凹槽中并排结合。并排分子识别的序列依赖于聚酰胺环与碱基的配对。在这项研究中，我们报告了一个数学模型，用于估计γ-氨基丁酸连接的聚酰胺与5- bp和6-bp DNA序列的结合自由能。采用最小二乘拟合方法对35个实验束缚常数进行了模型参数标定。该模型在交叉验证实验中表现良好，参数符合先前提出的聚酰胺- dna结合的经验规律。我们将该模型应用于目标聚酰胺的设计，评估所提出的聚酰胺与目标DNA序列结合的能力，同时最大限度地减少与剩余DNA序列的结合。
Three- and four-ring polyamides containingN-methylimidazole andN-methylpyrrole, and their hairpin-linked derivatives, bind side-by-side in the minor groove of DNA in a sequence-specific manner. The sequences recognized by side-by-side molecules are dependent on the pairings of the polyamide rings to the bases. In this study we report a mathematical model for estimating the free energies of binding for γ-aminobutyric acid-linked polyamides to 5- and 6-bp DNA sequences. The model parameters are calibrated by a least-squares fit to 35 experimental binding constants. The model performs well in cross-validation experiments and the parameters are consistent with previously proposed empirical rules of polyamide–DNA binding. We apply the model to the design of targeted polyamides, evaluating the ability of the proposed polyamides to bind to a DNA sequence of interest while minimizing binding to the remaining DNA sequences.