Refinement of the solution structure of the RNA-DNA hybrid 5'-[r(GCA)d(TGC)]-2

The solution conformation of the self-complementary RNA-DNA hybrid hexamer 5'-[r(GCA)d(TGC)]/sub 2/ is investigated by NMR spectroscopy and restrained molecular dynamics. The /sup 1/H-NMR spectrum is assigned in a sequential manner using two-dimensional homonuclear Hartmann-Hahn and nuclear Overhauser enhancement spectroscopy. From the latter a set of 178 approximate interproton distance restraints are determined and used as the basis of a structure refinement by restrained molecular dynamics. Eight independent calculations are carried out, four from a classical A-type geometry and four from a classical B-type one. Convergence is achieved to very similar A-type structures with an average atomic root mean square difference between them of 1.0 j 0.2 E. The converged structures exhibit variations in helical parameters similar to those found previously for the analogue RNA hexamer 5'-r(GCAUGC)/sub 2/