|Title||Toward an atomistic model for predicting transcription-factor binding sites.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Endres, RG, Schulthess, TC, Wingreen, NS|
|Date Published||2004 Nov 1|
|Keywords||Algorithms, Binding Sites, Computational Biology, Crystallography, X-Ray, DNA, DNA-Binding Proteins, Early Growth Response Protein 1, Immediate-Early Proteins, Models, Molecular, Pliability, Predictive Value of Tests, Protein Conformation, Software, Software Design, Transcription Factors|
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.