Olson W K, Babcock M S, Gorin A, Liu G, Marky N L, Martino J A, Pedersen S C, Srinivasan A R, Tobias I, Westcott T P
Department of Chemistry, Rutgers, State University of New Jersey, New Brunswick 08903, USA.
Biophys Chem. 1995 Jun-Jul;55(1-2):7-29. doi: 10.1016/0301-4622(94)00139-b.
DNA base sequence, once thought to be interesting only as a carrier of the genetic blueprint, is now recognized as playing a structural role in modulating the biological activity of genes. Primary sequences of nucleic acid bases describe real three-dimensional structures with properties reflecting those structures. Moreover, the structures are base sequence dependent with individual residues adopting characteristic spatial forms. As a consequence, the double helix can fold into tertiary arrangements, although the deformation is much more gradual and spread over a larger molecular scale than in proteins. As part of an effort to understand how local structural irregularities are translated at the macromolecular level in DNA and recognized by proteins, a series of calculations probing the structure and properties of the double helix have been performed. By combining several computational techniques, complementary information as well as a series of built-in checks and balances for assessing the significance of the findings are obtained. The known sequence dependent bending, twisting, and translation of simple dimeric fragments have been incorporated into computer models of long open DNAs of varying length and chemical composition as well as in closed double helical circles and loops. The extent to which the double helix can be forced to bend and twist is monitored with newly parameterized base sequence dependent elastic energy potentials based on the observed configurations of adjacent base pairs in the B-DNA crystallographic literature.
DNA碱基序列，曾经被认为仅仅作为遗传蓝图的载体才有意义，现在则被认为在调节基因的生物活性方面发挥着结构作用。核酸碱基的一级序列描述了具有反映这些结构特性的真实三维结构。此外，这些结构依赖于碱基序列，单个残基采用特征性的空间形式。因此，双螺旋可以折叠成三级结构，尽管这种变形比蛋白质中的变形更加渐进，且分布在更大的分子尺度上。作为理解局部结构不规则性如何在DNA的大分子水平上转化并被蛋白质识别的努力的一部分，已经进行了一系列探测双螺旋结构和性质的计算。通过结合多种计算技术，可以获得互补信息以及一系列用于评估研究结果重要性的内置检查和平衡机制。已知的简单二聚体片段依赖于序列的弯曲、扭曲和平移，已被纳入不同长度和化学组成的长开放DNA以及封闭双螺旋环和环的计算机模型中。基于B-DNA晶体学文献中相邻碱基对的观察构型，利用新参数化的依赖于碱基序列的弹性能量势来监测双螺旋被迫弯曲和扭曲的程度。
