Sequence-Structure Relationships and Information Readout in Double-Helical DNA

迪克森博士用X射线晶体学分析合成DNA 寡聚体，以了解碱基序列如何影响局部 螺旋结构的方式，可以有助于特定的 限制性内切酶、阻遏物和 其他控制蛋白质和抗肿瘤药物。 先前 他和其他人的工作表明，B-DNA比DNA更重要， 对序列扰动的敏感性高于A-DNA，而Z-DNA 最不敏感。 含有碱基对AT的B-DNA区域 有一个更窄，更深的小沟比GC或 混合序列区域，并提供更好的结合位点， 平面高分子抗肿瘤药物。 迪克森博士已经证明 狭窄的AT小沟包含了一个有序的Z字形 每个碱基对具有两个沃茨的水合作用脊，而 更宽的一般序列的小沟有带状的 水化作用沿着格罗夫的墙壁，同样是两个沃茨 每个碱基对 AT碱基对具有更大的螺旋桨扭曲 特别是如果一条链中有一连串的A 允许大沟交叉股氢键。 迪克森医生 打算检查几个晶体中的关键碱基序列 形式，以隔离晶体堆积的影响。 目标 是从碱基序列预测局部螺旋变形， 并学习如何设计网站， 特定药物或蛋白质。

Dr. Dickerson is using x-ray crystallography of synthetic DNA oligomers to learn how the base sequence influences local helix structure in a manner that can contribute to specific recognition of the DNA by restriction enzymes, repressors and other control proteins, and by antitumor drugs. Previous work by him and by others has shown that B-DNA is more sensitive to sequence perturbation than A-DNA, with Z-DNA least sensitive. Regions of B-DNA containing base pairs AT have a narrower and deeper minor groove than do GC or mixed-sequence regions, and provide better binding sites for planar polymeric antitumor drugs. Dr. Dickerson has shown that the narrow AT minor grooves contain an ordered, zig-zag spine of hydration with two waters per base pair, whereas wider general-sequence minor grooves have to ribbons of hydration down the walls of the grove, again with two waters per base pair. AT base pairs have greater propeller twist than GC, especially if a succession of A's in one strand permits major groove cross-strand H bonds. Dr. Dickerson intends to examine key base sequences in several crystal forms, to isolate the influence of crystal packing. The goal is to predict local helix deformations from base sequence, and learn how to design sites that will be recognized by specific drugs or proteins.