(156g) Molecular Simulation of RNA Tetraloop Formation

The RNA tetraloop is the smallest, simplest and the most frequent RNA motif, and is involved in numerous important biological functions. A similar structure, which is common in rhibosomal RNA and involves a single nucleotide deletion in the tetraloop, is analyzed using molecular simulation. This deletion-containing tetraloop also appears to play an important role in protein-RNA binding. Molecular simulation of these structures has provided insight into this structure's potential role as an intermediate structure in tetraloop formation, and how this intermediate is structurally stabilized. Reverse melting simulations suggest that this may be a kinetically trapped intermediate in the formation of the commonly observed tetraloop. These simulations suggest a mechanism for the tetraloop formation that is consistent with trapped structures in the rhibosomal RNA database. These structures from the database highlight the importance of a stem insertion in this intermediate. Molecular Dynamics of a particular deletion intermediate showed that specific hydrogen bonding between this stem insertion and both the loop and the stem is what stabilizes this intermediate. Additional conformational stabilization is derived from the insertion as well.