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Inherent DNA curvature and flexibility correlate with TATA box functionality
Author(s) -
Norberto de Souza Osmar,
Ornstein Rick L.
Publication year - 1998
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(199811)46:6<403::aid-bip5>3.0.co;2-a
Subject(s) - dodecameric protein , dna , chemistry , tata box , transcription (linguistics) , hmg box , duplex (building) , base pair , dna binding site , biophysics , molecular dynamics , transcription factor , computational biology , crystallography , dna binding protein , promoter , gene , biochemistry , biology , gene expression , computational chemistry , linguistics , philosophy
Four 1.5 ns molecular dynamics (MD) simulations were performed on the d(GCTATAAAAGGG) · d(CCCTTTTATAGC) double helix dodecamer bearing the Adenovirus major late promoter TATA element and three iso‐composition mutants for which physical and biochemical data are available from the same laboratory. Three of these DNA sequences experimentally induce tight binding with the TATA box binding protein (TBP) and induce high transcription rates; the other DNA sequence induces much lower TBP binding and transcription. The x‐ray crystal structures have previously shown that the duplex DNA in DNA–TBP complexes are highly bent. We performed and analyzed MD simulations for these four DNAs, whose experimental structures are not available, in order to address the issue of whether inherent DNA structure and flexibility play a role in establishing these observed preferences. A comparison of the experimental and simulated results demonstrated that DNA duplex sequence‐dependent curvature and flexibility play a significant role in TBP recognition, binding, and transcriptional activation. © 1998 John Wiley & Sons, Inc. Biopoly 46: 403–415, 1998