Correlations between the sugar-backbone conformation and the third strand orientation in triple helices

Abstract Molecular mechanics and molecular dynamics were used to study the structures of triplexes with a purine-rich third strand containing either GpA or ApG steps. Comparison was made between two models of a chemically homologous triplex which differ in the third strand orientation. Our calculations show that the third strand orientation has a major influence on the sugar-backbone conformation of the triplexes. For the antiparallel triplex, the equilibrium state is soon reached and small variations of the conformational parameters are detected during the molecular dynamics simulation. For the parallel triplex, a progressive reorganization of the phosphodiester chain is observed within the Watson-Crick duplex and several conformational transitions at the level of the sugar puckers and backbone torsion angles occur during the molecular dynamics run. The parallel triplex has a third strand hydrogen-bonding scheme that implies hydrogen-bond formation between the third strand bases and the two bases of the Watson-Crick pairs. The antiparallel triplex has a reverse-Hoogsteen hydrogen-bond pattern. For both triplexes, the hydrogen-bond bridge stabilities have been verified over 500 ps of the molecular dynamics simulation.