Stability and motion of a hairpin and the corresponding mismatched duplex: a theoretical exploration using molecular mechanics and normal mode analysis of 2D NMR results on d(GCCGCAGC)

The oligomer d(GCCGCAGC) can adopt two different conformations: i) a duplex with two mismatched A.C base pairs and ii) a hairpin with two C.G base pairs and a single stranded loop. We report molecular mechanics, normal mode analysis, and thermodynamic stability calculations for both structures. We show that the energy-minimized structure and harmonic-dynamics results are in complete agreement with the observed NOE spectrum and imino proton exchange data. We conclude that the high stability of the hairpin structure over the duplex at low salt concentration is due to the higher vibrational entropy contribution to the system free energy by the single stranded loop and to the lack of minor groove phosphate/phosphate electrostatic repulsions that tend to destabilize the duplex.