Olson W K, Gorin A A, Lu X J, Hock L M, Zhurkin V B
Department of Chemistry, Rutgers University, New Brunswick, NJ 08903, USA.
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11163-8. doi: 10.1073/pnas.95.19.11163.
The deformability of double helical DNA is critical for its packaging in the cell, recognition by other molecules, and transient opening during biochemically important processes. Here, a complete set of sequence-dependent empirical energy functions suitable for describing such behavior is extracted from the fluctuations and correlations of structural parameters in DNA-protein crystal complexes. These elastic functions provide useful stereochemical measures of the local base step movements operative in sequence-specific recognition and protein-induced deformations. In particular, the pyrimidine-purine dimers stand out as the most variable steps in the DNA-protein complexes, apparently acting as flexible "hinges" fitting the duplex to the protein surface. In addition to the angular parameters widely used to describe DNA deformations (i.e., the bend and twist angles), the translational parameters describing the displacements of base pairs along and across the helical axis are analyzed. The observed correlations of base pair bending and shearing motions are important for nonplanar folding of DNA in nucleosomes and other nucleoprotein complexes. The knowledge-based energies also offer realistic three-dimensional models for the study of long DNA polymers at the global level, incorporating structural features beyond the scope of conventional elastic rod treatments and adding a new dimension to literal analyses of genomic sequences.
双螺旋DNA的可变形性对于其在细胞中的包装、被其他分子识别以及在具有重要生化意义的过程中瞬时打开至关重要。在此，从DNA-蛋白质晶体复合物中结构参数的波动和相关性中提取出了一整套适用于描述此类行为的序列依赖性经验能量函数。这些弹性函数为序列特异性识别和蛋白质诱导的变形中起作用的局部碱基步移提供了有用的立体化学度量。特别地，嘧啶-嘌呤二聚体在DNA-蛋白质复合物中是最可变的步移，显然充当使双链体与蛋白质表面适配的柔性“铰链”。除了广泛用于描述DNA变形的角度参数（即弯曲角和扭转角）外，还分析了描述碱基对沿螺旋轴和横跨螺旋轴位移的平移参数。观察到的碱基对弯曲和剪切运动的相关性对于核小体和其他核蛋白复合物中DNA的非平面折叠很重要。基于知识的能量还为在全局水平上研究长DNA聚合物提供了逼真的三维模型，纳入了传统弹性杆处理范围之外的结构特征，并为基因组序列的文字分析增添了新的维度。
