Consecutive non-natural PZ nucleobase pairs in DNA impact helical structure as seen in 50 µs molecular dynamics simulations.
Nucleic Acids Res
; 45(7): 3643-3653, 2017 04 20.
Article
em En
| MEDLINE
| ID: mdl-28334863
ABSTRACT
Z Little is known about the influence of multiple consecutive 'non-standard' ( , 6-amino-5-nitro-2(1H)-pyridone, and , 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one) nucleobase pairs on the structural parameters of duplex DNA. nucleobase pairs follow standard rules for Watson-Crick base pairing but have rearranged hydrogen bonding donor and acceptor groups. Using the X-ray crystal structure as a starting point, we have modeled the motions of a DNA duplex built from a self-complementary oligonucleotide (5Î-CTTATPPPZZZATAAG-3Î) in water over a period of 50 µs and calculated DNA local parameters, step parameters, helix parameters, and major/minor groove widths to examine how the presence of multiple, consecutive nucleobase pairs might impact helical structure. In these simulations, the -containing DNA duplex exhibits a significantly wider major groove and greater average values of stagger, slide, rise, twist and h-rise than observed for a 'control' oligonucleotide in which nucleobase pairs are replaced by . The molecular origins of these structural changes are likely associated with at least two differences between and . First, the electrostatic properties of differ from in terms of density distribution and dipole moment. Second, differences are seen in the base stacking of pairs in dinucleotide steps, arising from energetically favorable stacking of the nitro group in with π-electrons of the adjacent base.
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Base de dados:
MEDLINE
Assunto principal:
DNA
/
Simulação de Dinâmica Molecular
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article