Statistical mechanics of sequence-dependent circular DNA and its application for DNA cyclization
Statistical mechanics of sequence-dependent circular DNA and its application for DNA cyclization
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DOI：
10.1016/s0006-3495(03)74838-3
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发表时间：
2003-01-01
影响因子：
3.4
通讯作者：
Crothers, DM
中科院分区：
文献类型：
--
作者：
Zhang, YL;Crothers, DM
DNA环化可能是系统定量序列依赖性DNA弯曲和柔性的最有力的方法。我们扩展了均匀的DNA环的统计力学模型，认为离散的碱基对，从而允许不均匀性，并应用该模型分析DNA环化。该理论从循环DNA的最小能量构型的迭代搜索开始。热力学量，如J因子，这基本上是圆形和线性形式的配分函数的比率，通过整合谐波近似下的配置周围的热波动进行评估。得到了均匀环状DNA在弯曲各向异性和非弯曲各向异性情况下平衡构型的精确解析表达式。评价了均质和非均质DNA的J因子。详细分析了DNA环化中的曲率、螺旋重复、弯曲和扭转柔性的影响，揭示了DNA环化可以检测到小至一度的曲率和几个百分比的柔性变化。新方法计算的J因子与Monte Carlo模拟结果吻合较好，而新理论计算效率更高。实验结果的模拟已被证明。
DNA cyclization is potentially the most powerful approach for systematic quantitation of sequence-dependent DNA bending and flexibility. We extend the statistical mechanics of the homogeneous DNA circle to a model that considers discrete basepairs, thus allowing for inhomogeneity, and apply the model to analysis of DNA cyclization. The theory starts from an iterative search for the minimum energy configuration of circular DNA. Thermodynamic quantities such as the J factor, which is essentially the ratio of the partition functions of circular and linear forms, are evaluated by integrating the thermal fluctuations around the configuration under harmonic approximation. Accurate analytic expressions are obtained for equilibrium configurations of homogeneous circular DNA with and without bending anisotropy. J factors for both homogeneous and inhomogeneous DNA are evaluated. Effects of curvature, helical repeat, and bending and torsional flexibility in DNA cyclization are analyzed in detail, revealing that DNA cyclization can detect as little as one degree of curvature and a few percent change in flexibility. J factors calculated by our new approach are well consistent with Monte Carlo simulations, whereas the new theory has much greater efficiency in computations. Simulation of experimental results has been demonstrated.