| DNA-binding proteins are involved in essential biological processes including gene expression, DNA packaging and DNA repair. They bind to DNA target sequences with different degrees of binding specificity, ranging from highly specific to non-specific. Alterations of DNA-binding specificity, due to either genetic variation or somatic mutations, can lead to various diseases. In this study, a comparative analysis of protein-DNA complex structures was carried out to investigate the structural features for binding specificity. The analysis was done using three curated datasets of protein-DNA complexes with different degrees of DNA-binding specificity: highly specific (HS), multi-specific (MS), and non-specific (NS). We found a clear trend of structural features among these three classes, including amino acid binding propensities, simple and complex hydrogen bonds, major groove and base contacts, DNA shape, and conformational changes upon DNA-binding. These structural features were then applied to assess the accuracy of TF-DNA docking predictions. A binary classifier for evaluating the prediction accuracy was developed using a training dataset and the structural features as well as three binding affinity scores. The results on a test dataset show much improved prediction accuracy over previous methods. |
