Conformational characteristics of DNA: Empirical classifications and a hypothesis for the conformational behaviour of dinucleotide steps
Conformational characteristics of DNA: Empirical classifications and a hypothesis for the conformational behaviour of dinucleotide steps
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DOI：
10.1098/rsta.1997.0002
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发表时间：
1997-01-15
期刊：
影响因子：
5
通讯作者：
Calladine, CR
中科院分区：
文献类型：
--
作者：
ElHassan, MA;Calladine, CR
本文研究了DNA的几何构型和结构，用X-射线衍射法测定了DNA的低聚物单晶结构。建立并仔细描述了60种裸（即不与任何蛋白质或药物结合）DNA寡聚体（25种十二聚体、18种十聚体、16种八聚体和1种四聚体）的原子坐标数据库。一个广泛的经验研究的几何形状的DNA二核苷酸步骤的数据库中，只涉及未修饰的沃森-克里克碱基对（A-T和G-C），报告，和一些新的相关性和分类进行了详细描述。的主要结论包括运动学分类的二核苷酸步骤分为两个主要类别：刚性和松散（或灵活或弹性）。“连续柔性”的步骤被示出为沿着良好定义的单自由度模式沿着锻炼它们的柔性，其中滚动、滑动和扭转都线性相关。刚性阶跃为AA/TT、AT和GA/TC，松散阶跃为GG/CC、GC、CG，而松散（连续柔性）阶跃为CA/TG和TA。AC/GT是所有步骤中最不明确的一个，也许最好将其描述为既不是刚性步骤，也不是松散步骤，而是一个“中间”步骤。基对参数也仔细检查和由此产生的平均螺旋桨和灵活性的步骤之间的关键相关性（等于幻灯片的标准差），我们最近在其他地方描述过（El哈桑& Calladine 1996），一个简单的两个-给出了描述糖磷酸骨架构象的参数方案，并用于将我们数据库中所有条目中的糖磷酸骨架分类为A-主链和B-主链构象。主链在确定二核苷酸步骤的构象偏好中的作用通过证明B-主链构象允许在卷曲/滑动/扭转构象空间中的相当窄的通道（所有三个参数线性相关）来检查，而A-主链仅允许在空间的高卷曲、低扭转、低滑动端附近的小“盒”区域。根据（a）与组成碱基对的螺旋桨扭转相关的机械堆积效应（螺旋桨-柔性相关性），（B）与特殊静电荷分布相关的化学堆积效应和均匀G/C台阶中的π-π效应（Hunter 1993），以及（c）在不存在（a）和（B）的情况下起支配作用的主链支配效应。
This paper is concerned with an investigation of the geometry and structure of DNA as revealed by X-ray diffraction of single crystal oligomeric structures. A database of atomic coordinates of 60 naked (i.e. not bound to any protein or drug) DNA oligomers (25 dodecamers, 18 decamers, 16 octamers and 1 tetramer) is set up and carefully described. An extensive empirical study of the geometries of DNA dinucleotide steps in the database, involving only unmodified Watson-Crick base pairs (A-T and G-C), is reported, and a number of new correlations and classifications are described in detail. The main conclusions include the kinematic classification of dinucleotide steps into two main classes: rigid and loose (or flexible or bistable). 'Continuously flexible' steps are shown to exercise their flexibility along a well-defined single-degree-of-freedom pattern, with roll, slide and twist all correlated linearly. The rigid steps are AA/TT, AT and GA/TC, and the loose (bistable) steps are GG/CC, GC, CG while the loose (continuously flexible) steps are CA/TG and TA. AC/GT is the least clear of all steps and it is perhaps best described as neither a rigid nor a loose step but rather an 'intermediate' step. The base-pair parameters are also carefully examined and the resulting pivotal correlation between the average propeller and the flexibility of the step (equals the standard deviation of slide), that we have recently described elsewhere (El Hassan & Calladine 1996), is examined in some detail.A simple two-parameter scheme for the description of the conformation of the sugar phosphate backbone is given and used to classify the sugar phosphate backbones in all entries of our database into A-backbone and B-backbone conformations. The role of the backbone in determining the conformational preferences of the dinucleotide steps is examined by demonstrating that whereas the B-backbone conformation permits a fairly narrow channel in the roll/slide/twist conformational space, with all three parameters linearly correlated, the A-backbone allows only a small 'box' region near the high-roll, low-twist, low-slide end of the space.Finally, the empirically determined conformational characteristics of the various dinucleotide steps are accounted for in terms of (a) mechanical stacking effects associated with propeller-twisting of constituent base pairs (the propeller-flexibility correlation), (b) chemical stacking effects associated with the special electrostatic charge distributions and pi-pi effects in homogeneous G/C steps (Hunter 1993), and (c) backbone-dictated effects that govern in the absence of (a) and (b).