Krueger Andrew, Protozanova Ekaterina, Frank-Kamenetskii Maxim D
Center for Advanced Biotechnology and Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
Biophys J. 2006 May 1;90(9):3091-9. doi: 10.1529/biophysj.105.078774. Epub 2006 Feb 24.
Preservation of genetic information in DNA relies on shielding the nucleobases from damage within the double helix. Thermal fluctuations lead to infrequent events of the Watson-Crick basepair opening, or DNA "breathing", thus making normally buried groups available for modification and interaction with proteins. Fluctuational basepair opening implies the disruption of hydrogen bonds between the complementary bases and flipping of the base out of the helical stack. Prediction of sequence-dependent basepair opening probabilities in DNA is based on separation of the two major contributions to the stability of the double helix: lateral pairing between the complementary bases and stacking of the pairs along the helical axis. The partition function calculates the basepair opening probability at every position based on the loss of two stacking interactions and one base-pairing. Our model also includes a term accounting for the unfavorable positioning of the exposed base, which proceeds through a formation of a highly constrained small loop, or a ring. Quantitatively, the ring factor is found as an adjustable parameter from the comparison of the theoretical basepair opening probabilities and the experimental data on short DNA duplexes measured by NMR spectroscopy. We find that these thermodynamic parameters suggest nonobvious sequence dependent basepair opening probabilities.
DNA中遗传信息的保存依赖于在双螺旋结构中保护核碱基免受损伤。热涨落会导致沃森-克里克碱基对偶尔打开，即DNA“呼吸”，从而使通常埋藏的基团可用于修饰以及与蛋白质相互作用。涨落性碱基对打开意味着互补碱基之间的氢键断裂以及碱基从螺旋堆积中翻转出来。DNA中序列依赖性碱基对打开概率的预测基于对双螺旋稳定性的两个主要贡献的分离：互补碱基之间的横向配对以及碱基对沿螺旋轴的堆积。配分函数基于两个堆积相互作用和一个碱基配对的损失来计算每个位置的碱基对打开概率。我们的模型还包括一个考虑暴露碱基不利定位的项，这种不利定位通过形成高度受限的小环或环来进行。定量地说，通过比较理论碱基对打开概率和核磁共振光谱测量的短DNA双链体的实验数据，将环因子作为一个可调参数来确定。我们发现这些热力学参数表明了非明显的序列依赖性碱基对打开概率。
