Fritsch V, Wolf R M
Central Research Laboratories Ciba-Geigy Ltd, Basel, Switzerland.
J Biomol Struct Dyn. 1994 Jun;11(6):1161-74. doi: 10.1080/07391102.1994.10508061.
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.
RNA-DNA杂交双链体与转录和复制等多种生物学机制相关。像核糖核酸酶H这样的酶能特异性切割RNA-DNA双链体中的RNA链。在反义技术中，mRNA与“修饰的”寡（脱氧）核苷酸复合会形成新的杂交双链体。在原子水平上了解结构和动力学行为对于理解任何涉及杂交双链体的过程至关重要。因此，对杂交双链体结构r(GA12G).d(CT12C)进行了分子动力学研究（200皮秒的轨迹）。在模拟过程中，脱氧核糖残基呈现出C2'-内向和C3'-内向之间的褶皱状态，平均模式为O4'-内向-C1'-外向，而RNA链的核糖则保持在C3'-内向褶皱区域。将结果与在相同模拟条件下对DNA-DNA双链体d(GA12G).d(CT12C)获得的结果进行比较。杂交双链体中的DNA链表现与标准B型DNA双链体中的相似。然而，杂交双链体的螺旋参数更接近A型而非B型。这些观察结果表明，RNA-DNA杂交双螺旋既不是清晰的A型也不是B型。两条链中的呋喃糖可以呈现不同的褶皱模式，而不会出现主要的几何限制。模拟结果与最近的实验数据高度吻合。
