A generalized conformational energy function of DNA derived from molecular dynamics simulations.
A generalized conformational energy function of DNA derived from molecular dynamics simulations.
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DOI：
10.1093/nar/gkp718
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发表时间：
2009-11
影响因子：
14.9
通讯作者：
Sarai A
中科院分区：
文献类型：
--
作者：
Yamasaki S;Terada T;Shimizu K;Kono H;Sarai A
蛋白质通过两种不同的机制识别DNA序列。第一种是直接读出，识别是通过蛋白质和DNA碱基之间的直接相互作用来调节的。第二种是间接读出，这是由于DNA结构的构象依赖性和可变形性对序列的依赖性造成的。已经提出了各种能量函数来评估间接读数对复杂地层中的自由能变化的贡献。我们开发了一个新的广义能量函数来估计DNA的变形性与序列的相关性。这个函数是从以前在B-DNA十二聚体上进行的分子动力学模拟得出的，每个B-DNA十二聚体的中心都嵌入了一个可能的四聚体序列。通过取四聚体中心碱基对步骤的基步参数的概率分布函数(PDF)的对数，它区分自然序列和随机序列的能力优于以前以调和形式逼近能量函数的方法。通过对这两种方法计算的能量分布的比较，我们发现调和近似对采用多重稳定构象的四聚体的构象能产生了显著的误差。
Proteins recognize DNA sequences by two different mechanisms. The first is direct readout, in which recognition is mediated by direct interactions between the protein and the DNA bases. The second is indirect readout, which is caused by the dependence of conformation and the deformability of the DNA structure on the sequence. Various energy functions have been proposed to evaluate the contribution of indirect readout to the free-energy changes in complex formations. We developed a new generalized energy function to estimate the dependence of the deformability of DNA on the sequence. This function was derived from molecular dynamics simulations previously conducted on B-DNA dodecamers, each of which had one possible tetramer sequence embedded at its center. By taking the logarithm of the probability distribution function (PDF) for the base-step parameters of the central base-pair step of the tetramer, its ability to distinguish the native sequence from random ones was superior to that with the previous method that approximated the energy function in harmonic form. From a comparison of the energy profiles calculated with these two methods, we found that the harmonic approximation caused significant errors in the conformational energies of the tetramers that adopted multiple stable conformations.
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影响因子：
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通讯作者：
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