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B-DNA TWISTING CORRELATES WITH BASE-PAIR MORPHOLOGY

机译:B-DNA扭曲与碱基对形态相关

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The observed sequence dependence of the mean twist angles in 38 B-DNA crystal structures can be understood in terms of simple geometrical features of the constituent base-pairs. Structures with low twist appear to unwind in response to severe steric clashes of large exocyclic groups (such as NH2-NH2) in the major and minor grooves, while those with high twist are subjected to lesser contacts (H-O and H-H). We offer a simple clash function that depends on base-pair morphology (i.e. the chemical constitution of base-pairs) and satisfactorily accounts for the twist angles of the ten common Watson-Crick dimer steps both in the solid state and in solution. The twist-clash correlation that we find here still holds when extended to modified bases. In addition to Calladine's purine-purine clashes, we add other close contacts between bases in the grooves, and consider the conformational restrictions on the geometry of the sugar-phosphate backbone (namely, we emphasize the tendency of DNA to conserve virtual backbone length). The significance of this finding is threefold: (1) sequence-dependent DNA twisting is directly involved in protein-DNA interactions; (2) strong correlation between Twist and Roll helps to elucidate the bending of the double helix as a function of base sequence; (3) it is possible to anticipate the effects of chemical modifications on twisting and bending. The mutual correlations of other structural parameters with the twist make this angle a primary determinant of DNA conformational heterogeneity. [References: 93]
机译:可以从组成碱基对的简单几何特征来理解38 B-DNA晶体结构中平均扭转角的序列依赖性。低扭曲的结构似乎在大槽和小槽中响应大的外环基团(例如NH2-NH2)的严重空间碰撞而解开,而高扭曲的结构则受到较小的接触(H-O和H-H)。我们提供了一个简单的碰撞函数,该函数取决于碱基对的形态(即碱基对的化学组成),并令人满意地说明了固态和溶液中十个常见的Watson-Crick二聚体步骤的扭曲角。当扩展到修改后的基数时,我们在这里仍然可以找到扭曲冲突相关性。除了Calladine的嘌呤-嘌呤碰撞之外,我们还在凹槽的碱基之间添加了其他紧密接触,并考虑了糖-磷酸骨架的几何构象限制(即,我们强调了DNA保留虚拟骨架长度的趋势)。这一发现的意义有三方面:(1)序列依赖性DNA扭曲直接参与蛋白质-DNA相互作用; (2)扭曲和滚动之间的强相关性有助于阐明双螺旋的弯曲与碱基序列的关系; (3)可以预期化学修饰对扭曲和弯曲的影响。其他结构参数与扭曲的相互关系使该角度成为DNA构象异质性的主要决定因素。 [参考:93]

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