Expansion of trinucleotide repeat DNA of the classes CAGÃ?Â·CTG, CGGÃ?Â·CCG and GAAÃ?Â·TTC are found to be associated with several neurodegenerative disorders. Different mechanisms have been attributed to the expansion of triplets, mainly involving the formation of alternate secondary structures by such repeats. This paper reports the molecular dynamics simulation of triplet repeat DNA sequences to study the basic structural features of DNA that are responsible for the formation of structures such as hairpins and slip-strand DNA leading to expansion. All the triplet repeat sequences studied were found to be more flexible compared to the control sequence unassociated with disease. Moreover, flexibility was found to be in the order CAGÃ?Â·CTG > CGGÃ?Â·CCG = GAAÃ?Â·TTC, the highly flexible CAGÃ?Â·CTG repeat being the most common cause of neurodegenerative disorders. In another simulation, a single GÃ?Â·C to TÃ?Â·A mutation at the 9th position of the CAGÃ?Â·CTG repeat exhibited a reduction in bending compared to the pure 15-mer CAGÃ¢ï¿½Â¢CTG repeat. EPM1 dodecamer repeat associated with the pathogenesis of progressive myoclonus epilepsy was also simulated and showed flexible nature suggesting a similar expansion mechanism.
|Number of pages||17|
|Journal||Journal of Biomolecular Structure & Dynamics|
|Publication status||Published - Dec 2001|
ASJC Scopus subject areas
- Molecular Biology
- Structural Biology
Jithesh, P., Singh, P., & Joshi, R. R. (2001). Molecular dynamics studies of trinucleotide repeat DNA involved in neurodegenerative disorders. Journal of Biomolecular Structure & Dynamics, 19(3)(3), 479-495.