Endres Robert G, Schulthess Thomas C, Wingreen Ned S
Center for Computational Sciences and Computer Science & Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6164, USA.
Proteins. 2004 Nov 1;57(2):262-8. doi: 10.1002/prot.20199.
Identifying the specific DNA-binding sites of transcription-factor proteins is essential to understanding the regulation of gene expression in the cell. Bioinformatics approaches are fast compared to experiments, but require prior knowledge of multiple binding sites for each protein. Here, we present an atomistic force-field method to predict binding sites based only on the X-ray structure of a related bound complex. Specific flexible contacts between the protein and DNA are modeled by a library of amino acid side-chain rotamers. Using the example of the mouse transcription factor, Zif268, a well-studied zinc-finger protein, we show that the protein sequence alone, without the detailed experimental structure, gives a strong bias toward the consensus binding site.
识别转录因子蛋白的特定DNA结合位点对于理解细胞中基因表达的调控至关重要。与实验相比，生物信息学方法速度更快，但需要每种蛋白质多个结合位点的先验知识。在此，我们提出一种仅基于相关结合复合物的X射线结构来预测结合位点的原子力场方法。蛋白质与DNA之间的特定柔性接触通过氨基酸侧链旋转异构体文库进行建模。以小鼠转录因子Zif268（一种经过充分研究的锌指蛋白）为例，我们表明仅蛋白质序列，无需详细的实验结构，就对共有结合位点有强烈的偏好。
