Creating PWMs of transcription factors using 3D structure-based computation of protein-DNA free binding energies

Background: Knowledge of transcription factor-DNA binding patterns is crucial for understanding gene transcription. Numerous DNA-binding proteins are annotated as transcription factors in the literature, however, for many of them the corresponding DNA-binding motifs remain uncharacterized. Results: The position weight matrices (PWMs) of transcription factors from different structural classes have been determined using a knowledge-based statistical potential. The scoring function calibrated against crystallographic data on protein-DNA contacts recovered PWMs of various members of widely studied transcription factor families such as p53 and NF-B. Where it was possible, extensive comparison to experimental binding affinity data and other physical models was made. Although the p50p50, p50RelB, and p50p65 dimers belong to the same family, particular differences in their PWMs were detected, thereby suggesting possibly different in vivo binding modes. The PWMs of p63 and p73 were computed on...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Denitsa Alamanova, Philip Stegmaier, Alexander E. Kel
• Keywords: BMCBI 2010, Corresponding Dna-binding Motifs, Position Weight, Transcription Factor