Three-dimensional structures of small RNA molecules

The three-dimensional structures of RNA molecules are investigated using both theoretical methods such as Molecular Modeling, Molecular Mechanics or Molecular Dynamics, and NMR spectroscopy. Secondary structure prediction, either in terms of the ground state or in terms of the partition function of the Boltzmann ensembles of all structures, serve as starting points for the 3D structure prediction. The double helical stacks are introduced into the computations with constant geometries as determined by the base pairing patterns of the secondary structures. In the case of small RNA molecules with up to 30 nucleotides that lack extremely flexible structural elements (such as large loops, joints, or long free ends) we are considering to calculate the minimum free energy structures by means of direct energy minimization. Preliminary tests with small hairpin molecules with three- or four-base loops and chain lengths of 11 and 12 bases, respectively, showed two major outcomes:

• the structures are in good agreement with existing experimental data for the same three- and four-base loops, and
• the geometries of all optimized structures follow a common principle of minimizing the contact surface between the heterocyclic bases and the solvent.