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Consecutive non-natural PZ nucleobase pairs in DNA impact helical structure as seen in 50 μs molecular dynamics simulations

Molt, Robert, Georgiadis, Millie M. and Richards, Nigel G. J. 2017. Consecutive non-natural PZ nucleobase pairs in DNA impact helical structure as seen in 50 μs molecular dynamics simulations. Nucleic Acids Research 45 (7) , pp. 3643-3653. 10.1093/nar/gkx144

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Abstract

Little is known about the influence of multiple consecutive ‘non-standard’ (Z, 6-amino-5-nitro-2(1H)-pyridone, and P, 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one) nucleobase pairs on the structural parameters of duplex DNA. P:Z 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 (5΄-CTTATPPPZZZATAAG-3΄) 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 P:Z nucleobase pairs might impact helical structure. In these simulations, the PZ-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 P:Z nucleobase pairs are replaced by G:C. The molecular origins of these structural changes are likely associated with at least two differences between P:Z and G:C. First, the electrostatic properties of P:Z differ from G:C in terms of density distribution and dipole moment. Second, differences are seen in the base stacking of P:Z pairs in dinucleotide steps, arising from energetically favorable stacking of the nitro group in Z with π–electrons of the adjacent base.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Oxford University Press
ISSN: 0305-1048
Date of First Compliant Deposit: 29 March 2017
Date of Acceptance: 24 February 2017
Last Modified: 24 Jul 2017 13:51
URI: http://orca.cf.ac.uk/id/eprint/99478

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