CORRELATIONS BETWEEN THE SUGAR-BACKBONE CONFORMATION AND THE 3RD STRAND ORIENTATION IN TRIPLE HELICES

Molecular mechanics and molecular dynamics were used to study the stru ctures of triplexes with a purine-rich third strand containing either GpA or ApG steps. Comparison was made between two models of a chemical ly homologous tripler which differ in the third strand orientation. Ou r calculations show that the third strand orientation has a major infl uence on the sugar-backbone conformation of the triplexes. For the ant iparallel tripler, the equilibrium state is soon reached and small var iations of the conformational parameters are detected during the molec ular dynamics simulation. For the parallel tripler, a progressive reor ganization of the phosphodiester chain is observed within the Watson-C rick duplex and several conformational transitions at the level of the sugar puckers and backbone torsion angles occur during the molecular dynamics run. The parallel tripler 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 tr ipler has a reverse-Hoogsteen hydrogen-bond pattern. For both triplexe s, the hydrogen-bond bridge stabilities have been verified over 500 ps of the molecular dynamics simulation.