Exact method for numerically analyzing a model of local denaturation in superhelically stressed DNA
Exact method for numerically analyzing a model of local denaturation in superhelically stressed DNA
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DOI：
10.1103/physreve.59.3408
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发表时间：
1999-03-01
影响因子：
2.4
通讯作者：
Benham, CJ
中科院分区：
文献类型：
--
作者：
Fye, RM;Benham, CJ
局部变性，即在DNA双螺旋的两条链的特定位点处分离，是生物学中最基本的过程之一，需要允许在DNA转录和复制中读取碱基序列。在活的生物体中，这个过程可以通过调节施加在DNA上的超螺旋应力的量的酶来介导。我们提出了一个数值精确的技术分析超螺旋应力DNA的变性模型。这种方法是能够预测的位置和程度的过渡在环状超螺旋DNA分子的酶长度和指定的碱基对序列。它也可以用于通常在体内发现的DNA的闭合环，其为长链。该分析方法包括一个集成的DNA扭曲自由度，然后引入辅助变量解耦的自由度，这允许使用的传递矩阵法。算法实现我们的技术需要O（N-2）的操作和O（N）的内存来分析一个包含N个碱基对的DNA结构域。然而，为了分析DNA分子的长度，它必须在高精度浮点运算中实现。一个加速算法是通过对在一个状态下可以同时变性的碱基对的数量施加一个上界M来构造的。这种加速算法需要O（MN）的操作，并有一个分析有界的错误。实例计算表明，它实现了高精度（大于15位十进制数）与相对较小的值dl（M
Local denaturation, the separation at specific sites of the two strands comprising the DNA double helix, is one of the most fundamental processes in biology, required to allow the base sequence to be read both in DNA transcription and in replication. In living organisms this process can be mediated by enzymes which regulate the amount of superhelical stress imposed on the DNA. We present a numerically exact technique for analyzing a model of denaturation in superhelically stressed DNA. This approach is capable of predicting the locations and extents of transition in circular superhelical DNA molecules of kilobase lengths and specified base pair sequences. It can also be used for closed loops of DNA which are typically found in vivo to be kilobases long. The analytic method consists of an integration over the DNA twist degrees of freedom followed by the introduction of auxiliary variables to decouple the remaining degrees of freedom, which allows the use of the transfer matrix method. The algorithm implementing our technique requires O(N-2) operations and O(N) memory to analyze a DNA domain containing N base pairs. However, to analyze kilobase length DNA molecules it must be implemented in high precision floating point arithmetic. An accelerated algorithm is constructed by imposing an upper bound M on the number of base pairs that can simultaneously denature in a state. This accelerated algorithm requires O(MN) operations, and has an analytically bounded error. Sample calculations show that it achieves high accuracy (greater than 15 decimal digits) with relatively small values of dl (M