Structure and Hybridization Properties of Glycine Morpholine Oligomers in Complexes with DNA and RNA: Experimental and Molecular Dynamics Studies.

ABSTRACT

Methylenecarboxamide (glycine) morpholine oligomers (gMOs) with a modified backbone are new and promising nucleic acid analogues. In this work, a combination of circular dichroism spectroscopy, optical melting, and molecular dynamics simulations was used to investigate hybridization properties of gMOs, as well as the structure and dynamics of their tandem complexes with DNA and RNA. It was shown that the structure of nucleic acids in modified complexes is similar to that of the fully native analogues. The energies of binding and cooperative interactions at the helix-helix interface in the nick were determined experimentally and by computer simulation analysis. Here, we found for the first time, the possibility to determine and predict precisely the thermodynamic parameters of complementary complex formation using the original experimental and computer simulation approaches. It was shown that the use of simulation data in the explicit solvent and the molecular mechanics Poisson-Boltzmann (or generalized Born) surface area methods for the calculation of the hybridization enthalpy makes it possible to evaluate the thermal stability of DNA and gMO tandem duplexes with DNA or RNA with an unexpectedly high accuracy. We found that at high ionic strength and neutral pH, the observed thermal stability of the gMO/RNA tandem complex is similar to that of DNA/DNA and lower than that of gMO/DNA which is close to that of DNA/RNA.