Garel Thomas, Orland Henri
Service de Physique Théorique, CEA/DSM/SPhT, Unité de recherche associée au CNRS, 91191 Gif-sur-Yvette cedex, France.
Biopolymers. 2004 Dec 15;75(6):453-67. doi: 10.1002/bip.20140.
The Poland-Scheraga (PS) model for the helix-coil transition of DNA considers the statistical mechanics of the binding (or hybridization) of two complementary strands of DNA of equal length, with the restriction that only bases with the same index along the strands are allowed to bind. In this article, we extend this model by relaxing these constraints: We propose a generalization of the PS model that allows for the binding of two strands of unequal lengths N1 and N2 with unrelated sequences. We study in particular (i) the effect of mismatches on the hybridization of complementary strands, (ii) the hybridization of noncomplementary strands (as resulting from point mutations) of unequal lengths N1 and N2. The use of a Fixman-Freire scheme scales down the computational complexity of our algorithm from O(N1(2)N2(2) to O(N1N2). The simulation of complementary strands of a few kilo base pairs yields results almost identical to the PS model. For short strands of equal or unequal lengths, the binding displays a strong sensitivity to mutations. This model may be relevant to the experimental protocol in DNA microarrays, and more generally to the molecular recognition of DNA fragments. It also provides a physical implementation of sequence alignments.
用于DNA螺旋-卷曲转变的波兰-谢拉加（PS）模型考虑了等长的两条互补DNA链结合（或杂交）的统计力学，限制条件是沿链仅允许具有相同索引的碱基相互结合。在本文中，我们通过放宽这些限制来扩展该模型：我们提出了PS模型的一个推广，它允许长度分别为N1和N2且序列不相关的两条链进行结合。我们特别研究了（i）错配对互补链杂交的影响，（ii）长度为N1和N2的不等长非互补链（由点突变产生）的杂交。使用菲克斯曼-弗雷雷方案将我们算法的计算复杂度从O(N1²N2²)降低到O(N1N2)。几千碱基对的互补链模拟产生的结果几乎与PS模型相同。对于等长或不等长的短链，结合对突变表现出很强的敏感性。该模型可能与DNA微阵列中的实验方案相关，更广泛地说与DNA片段的分子识别相关。它还提供了序列比对的一种物理实现方式。
