Consecutive non-natural PZ nucleobase pairs in DNA impact helical structure as seen in 50 μs molecular dynamics simulations.
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 (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 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.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.|School of Chemistry, Cardiff University, Cardiff, CF10 3AT, UK.|Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.|ENSCO, Inc., 4849 North Wickham Road, Melbourne, FL 32940, USA.
Robert W
RW
Molt
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.|Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Millie M
MM
Georgiadis
School of Chemistry, Cardiff University, Cardiff, CF10 3AT, UK.
Nigel G J
NGJ
Richards
D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D044704:DNA, A-Form / Q000737:chemistry; D059371:DNA, B-Form / Q000737:chemistry; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D055672:Static Electricity
D044704:DNA, A-Form; D059371:DNA, B-Form; D009841:Oligonucleotides; D004247:DNA