TY - JOUR
T1 - Molecular dynamics studies of trinucleotide repeat dna involved in neurodegenerative disorders
AU - Jithesh, P. V.
AU - Singh, Prachi
AU - Joshi, Rajendra R.
PY - 2001/12
Y1 - 2001/12
N2 - Expansion of trinucleotide repeat DNA of the classes CAG•CTG, CGG•CCG and GAA•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 CAG•CTG > CGG•CCG ≈GAA•TTC, the highly flexible CAG•CTG repeat being the most common cause of neurodegenerative disorders. In another simulation, a single G•C to T•A mutation at the 9th position of the CAG•CTG repeat exhibited a reduction in bending compared to the pure 15-mer CAG/CTG repeat. EPM1 dode- camer repeat associated with the pathogenesis of progressive myoclonus epilepsy was also simulated and showed flexible nature suggesting a similar expansion mechanism.
AB - Expansion of trinucleotide repeat DNA of the classes CAG•CTG, CGG•CCG and GAA•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 CAG•CTG > CGG•CCG ≈GAA•TTC, the highly flexible CAG•CTG repeat being the most common cause of neurodegenerative disorders. In another simulation, a single G•C to T•A mutation at the 9th position of the CAG•CTG repeat exhibited a reduction in bending compared to the pure 15-mer CAG/CTG repeat. EPM1 dode- camer repeat associated with the pathogenesis of progressive myoclonus epilepsy was also simulated and showed flexible nature suggesting a similar expansion mechanism.
UR - http://www.scopus.com/inward/record.url?scp=0035702197&partnerID=8YFLogxK
U2 - 10.1080/07391102.2001.10506756
DO - 10.1080/07391102.2001.10506756
M3 - Article
C2 - 11790146
AN - SCOPUS:0035702197
SN - 0739-1102
VL - 19
SP - 479
EP - 495
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
IS - 3
ER -