OBSERVATION OF AN A-DNA TO B-DNA TRANSITION IN A NONHELICAL NUCLEIC-ACID HAIRPIN MOLECULE USING MOLECULAR-DYNAMICS

One of the truly challenging problems for molecular dynamics (MD) simu lations is demonstrating that the trajectories can sample not only in the vicinity of an experimentally determined structure, but also that the trajectories can find the correct experimental structure starting from some other structure. Frequently these transitions to the correct structure require that the simulations overcome energetic barriers to conformational change, Here we present unrestrained molecular dynamic s simulations of the DNA analogs of the RNA 5'-GGACUUCGGUCC-3' hairpin tetraloop. In one simulation we have used deoxyuracil residues, and i n the other we have used the native DNA deoxythymine residues, We demo nstrate that, on a nanosecond time scale, MD is able to simulate the t ransitions of both of the A-DNA stems to B-DNA stems within the constr aints imposed by the four-base loop that caps the helix. These results suggest that we are now in a position to use MD to address the nature of sequence-dependent structural effects in nonduplex DNA structures.