title: Theoretical studies on the intermolecular interactions of potentially primordial base-pair analogues.
abstract: Recent experimental studies on the Watson-Crick type base pairing of triazine and aminopyrimidine derivatives suggest that acid/base properties of the constituent bases might be related to the duplex stabilities measured in solution. Herein we use high-level quantum chemical calculations and molecular dynamics simulations to evaluate the base pairing and stacking interactions of seven selected base pairs, which are common in that they are stabilized by two N-H...O hydrogen bonds separated by one N-H...N hydrogen bond. We show that neither the base pairing nor the base stacking interaction energies correlate with the reported pK(a) data of the bases and the melting points of the duplexes. This suggests that the experimentally observed correlation between the melting point data of the duplexes and the pK(a) values of the constituent bases is not rooted in the intrinsic base pairing and stacking properties. The physical chemistry origin of the observed experimental correlation thus remains unexplained and requires further investigations. In addition, since our calculations are carried out with extrapolation to the complete basis set of atomic orbitals and with inclusion of higher electron correlation effects, they provide reference data for stacking and base pairing energies of non-natural bases.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265, Brno, Czech Republic. judit@ncbr.chemi.muni.cz
authors.forename: Judit E
authors.initials: JE
authors.lastname: Sponer
authors.forename: Alvaro
authors.initials: A
authors.lastname: Vázquez-Mayagoitia
authors.forename: Bobby G
authors.initials: BG
authors.lastname: Sumpter
authors.forename: Jerzy
authors.initials: J
authors.lastname: Leszczynski
authors.forename: Jirí
authors.initials: J
authors.lastname: Sponer
authors.forename: Michal
authors.initials: M
authors.lastname: Otyepka
authors.forename: Pavel
authors.initials: P
authors.lastname: Banás
authors.forename: Miguel
authors.initials: M
authors.lastname: Fuentes-Cabrera
mesh_terms: D020029:Base Pairing; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis*; D011789:Quantum Theory; D012313:RNA / Q000737:chemistry; D014227:Triazines / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D011743:Pyrimidines; D014227:Triazines; D012313:RNA; D004247:DNA; C030986:pyrimidine