Srinivasan A R, Torres R, Clark W, Olson W K
Department of Chemistry, Rutgers, State University of New Jersey, New Brunswick 08903.
J Biomol Struct Dyn. 1987 Dec;5(3):459-96. doi: 10.1080/07391102.1987.10506409.
A series of potential energy calculations have been carried out to estimate base sequence dependent structural differences in B-DNA. Attention has been focused on the simplest dimeric fragments that can be used to build long chains, computing the energy as a function of the orientation and displacement of the 16 possible base pair combinations within the double helix. Calculations have been performed, for simplicity, on free base pairs rather than complete nucleotide units. Conformational preferences and relative flexibilities are reported for various combinations of the roll, tilt, twist, lateral displacement, and propeller twist of individual residues. The predictions are compared with relevant experimental measures of conformation and flexibility, where available. The energy surfaces are found to fit into two distinct categories, some dimer duplexes preferring to bend in a symmetric fashion and others in a skewed manner. The effects of common chemical substitutions (uracil for thymine, 5-methyl cytosine for cytosine, and hypoxanthine for guanine) on the preferred arrangements of neighboring residues are also examined, and the interactions of the sugar-phosphate backbone are included in selected cases. As a first approximation, long range interactions between more distant neighbors, which may affect the local chain configuration, are ignored. A rotational isomeric state scheme is developed to describe the average configurations of individual dimers and is used to develop a static picture of overall double helical structure. The ability of the energetic scheme to account for documented examples of intrinsic B-DNA curvature is presented, and some new predictions of sequence directed chain bending are offered.
已经进行了一系列势能计算，以估计B-DNA中依赖于碱基序列的结构差异。研究重点是可用于构建长链的最简单二聚体片段，计算双螺旋内16种可能碱基对组合的取向和位移的能量函数。为简化起见，计算是在游离碱基对上进行的，而不是完整的核苷酸单元。报告了各个残基的滚动、倾斜、扭转、横向位移和螺旋桨扭转的各种组合的构象偏好和相对柔韧性。如有可用数据，将预测结果与相关的构象和柔韧性实验测量结果进行比较。发现能量表面可分为两类，一些二聚体双链体倾向于以对称方式弯曲，而另一些则以倾斜方式弯曲。还研究了常见化学取代（尿嘧啶取代胸腺嘧啶、5-甲基胞嘧啶取代胞嘧啶、次黄嘌呤取代鸟嘌呤）对相邻残基优先排列的影响，并在选定情况下纳入了糖磷酸骨架的相互作用。作为初步近似，忽略了可能影响局部链构型的更远距离邻居之间的长程相互作用。开发了一种旋转异构体状态方案来描述单个二聚体的平均构型，并用于构建整体双螺旋结构的静态图像。展示了能量方案解释已记录的固有B-DNA曲率示例的能力，并提供了一些关于序列导向链弯曲的新预测。
