title: A DFT study of 2-aminopurine-containing dinucleotides: prediction of stacked conformations with B-DNA structure.
abstract: The fluorescence properties of dinucleotides incorporating 2-aminopurine (2AP) suggest that the simplest oligonucleotides adopt conformations similar to those found in duplex DNA. However, there is a lack of structural data for these systems. We report a density functional theory (DFT) study of the structures of 2AP-containing dinucleotides (deoxydinucleoside monophosphates), including full geometry optimisation of the sugar-phosphate backbone. Our DFT calculations employ the M06-2X functional for reliable treatment of dispersion interactions and include implicit aqueous solvation. Dinucleotides with 2AP in the 5'-position and each of the natural bases in the 3'-position are examined, together with the analogous 5'-adenine-containing systems. Computed structures are compared in detail with typical B-DNA base-step parameters, backbone torsional angles and sugar pucker, derived from crystallographic data. We find that 2AP-containing dinucleotides adopt structures that closely conform to B-DNA in all characteristic parameters. The structures of 2AP-containing dinucleotides closely resemble those of their adenine-containing counterparts, demonstrating the fidelity of 2AP as a mimic of the natural base. As a first step towards exploring the conformational heterogeneity of dinucleotides, we also characterise an imperfectly stacked conformation and one in which the bases are completely unstacked.
authors.affiliation: EaStCHEM School of Chemistry, The University of Edinburgh, David Brewster Road, Edinburgh, EH9 3FJ, UK. a.c.jones@ed.ac.uk.
authors.forename: Darren A
authors.initials: DA
authors.lastname: Smith
authors.affiliation: EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
authors.forename: Leo F
authors.initials: LF
authors.lastname: Holroyd
authors.affiliation: EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
authors.forename: Tanja
authors.initials: T
authors.lastname: van Mourik
authors.affiliation: EaStCHEM School of Chemistry, The University of Edinburgh, David Brewster Road, Edinburgh, EH9 3FJ, UK. a.c.jones@ed.ac.uk.
authors.forename: Anita C
authors.initials: AC
authors.lastname: Jones
mesh_terms: D015075:2-Aminopurine / Q000737:chemistry*; D059371:DNA, B-Form / Q000737:chemistry*; D015226:Dinucleoside Phosphates / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D059371:DNA, B-Form; D015226:Dinucleoside Phosphates; D009841:Oligonucleotides; D015075:2-Aminopurine