BIOPHYSICAL THEORY AND MODELING |
Profiling the thermodynamic softness of adenoviral promoters
Chu Hwan Choi 1*, Zoi Rapti 1, Vladimir Gelev 1, Michele R. Hacker 1, Boian Alexandrov 2, Evelyn J Park 1, Jae Suk Park 1, Nobuo Horikoshi 3, Augusto Smerzi 2, Kim O Rasmussen 2, Alan R Bishop 2 and Anny Usheva 1
1 Beth Israel Deaconess Medical Center
2 Los Alamos National Laboratory
3 Washington University School of Medicine
* To whom correspondence should be addressed. E-mail: cchoi{at}bidmc.harvard.edu.
Submitted on October 10, 2007
Revised on November 21, 2007
Accepted on 18 March 2008
 |
Abstract |
|---|
We previously demonstrated that anharmonic DNA dynamical features correlate with transcriptional activity in selected viral promoters, and hypothesized that areas of DNA softness may represent loci of functional significance. The nine known promoters from human adenovirus type 5 were analyzed for inherent DNA softness using the Peyrard-Bishop-Dauxois (PBD) model and a statistical mechanics approach, utilizing a transfer integral operator (TIO). We found a loosely-defined pattern of softness peaks distributed both upstream and downstream of the transcriptional start sites, and that early transcriptional regions tended to be softer than late promoter regions. When reported transcription factor binding sites were superimposed on our calculated softness profiles, we observed a close correspondence in many cases, which suggests that DNA duplex breathing dynamics may play a role in protein recognition of specific nucleotide sequences and protein-DNA binding. These results suggest that genetic information is stored not only in explicit codon sequences, but also may be encoded into local dynamic and structural features, and that it may be possible to access this obscured information using DNA dynamics calculations.
Key Words:
Adenovirus, DNA dynamics, gene promoters
