A detailed interpretation of OH radical footprints in a TBP-DNA complex reveals the role of dynamics in mechanism of sequence-specific binding

Nina Pastor, Harel Weinstein, Elizabeth Jamison, Michael Brenowitz

Research output: Contribution to journalArticle

116 Scopus citations


The hydroxyl radical footprint of the TATA-binding protein (TBP) bound to the high-affinity sequence TATAAAAG of the adenovirus 2 major late promoter has been quantitatively compared to a 2 ns molecular dynamics simulation of the complex in aqueous solution at room temperature using the CHARMM23 potential. The nucleotide-by-nucleotide analysis of the TBP-TATA hydroxyl radical footprint correlates with the solvent-accessible surface calculated from the dynamics simulation. The results suggest that local reactivity towards OH radicals results from the interplay between the local DNA geometry imposed by TBP binding, and the dynamics of the side-chains contacting the sugar hydrogen atoms. Analysis of the dynamics suggests that, over time, TBP forms stable interactions with the sugar-phosphate backbone through multiple contacts to different partners. This mechanism results in an enthalpic advantage to complex formation at a low entropic cost. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)55-68
Number of pages14
JournalJournal of Molecular Biology
Issue number1
Publication statusPublished - Nov 17 2000



  • Entropy/enthalpy compensation
  • Molecular dynamics
  • Transcription

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this