Abstract
Quantum mechanics, molecular dynamics and statistical mechanics methods are used to analyze the importance of neutral Hoogsteen-wobble G.C pairing in the stabilization of triple helices based on the poly-(G.C-C) trio at neutral pH and low ionic strength. In spite of the existence of a single hydrogen bond, the Hoogsteen-wobble G.C pair is found to be quite stable both in gas phase and solvated DNA. Molecular dynamics simulations of different triplexes based on the d(G.C-C) trio leads to stable structures if the neutral d(G.C-C) steps stabilized by Hoogsteen-wobble pairs are mixed with d(G.C-C+) steps. Finally, high level ab initio calculations and thermodynamic integration techniques are used to determine the relative stability of G.C wobble and G.C imino pairings. It is found that triplexes containing the imino pairing are slightly more stable structures than those with the wobble one, due mainly to a better stacking.