Molecular dynamics simulations of a r(GA12G).d(CT12C) hybrid duplex.

RNA.DNA hybrid duplexes are relevant in various biological mechanisms like transcription and replication. Enzymes like RNase H cleave specifically the RNA strand in RNA.DNA duplexes. In antisense technology the complexation of mRNA with "modified" oligo(deoxy)-nucleotides leads to new hybrid duplexes. The knowledge about structure and dynamical behavior on an atomic level is fundamental for the understanding of any process involving hybrid duplexes. Therefore, molecular dynamics studies (200 picoseconds of trajectory) on a hybrid duplex structure r(GA12G).d(CT12C) were performed. During the stimulations, the deoxyribose residues assumed a puckering state between C2'-endo and C3'-endo, with an average mode around O4'-endo-C1'-exo, whereas the riboses of the RNA strand remained in the C3'-endo puckering domain. The results are compared to those obtained for the DNA.DNA duplex d(GA12G).d(CT12C) under identical simulation conditions. The DNA strand in the hybrid duplex behaves similar to that in a standard B-type DNA duplex. The helical parameters of the hybrid duplex however are closer to A- than to B-type. These observations suggest that RNA.DNA hybrid double helices are neither clearly A-form nor B-form. The furanoses in both strands can assume different puckering modes without the appearance of major geometrical constraints. The simulation results are in excellent agreement with recent experimental data.