Book of Abstracts: Albany 2003
June 17-21 2003
Molecular Dynamics Studies of RNA Hexaloop Stabilization by Base Interaction and Hydration
In vivo and in vitro experiments reveal the important role of RNA loop structures in the recognition and formation of functional RNA-RNA and RNA-protein complexes.
The interaction between the TAR RNA element, present at the 5?-end of all HIV-1 mRNAs, and the Tat-1 protein is one of the crucial steps in the HIV-1 replication cycle. The understanding of the TAR RNA structure and its recognition by the argininamide, peptides, or fragments of the Tat-1 protein, is advanced and of importance for design of potential anti-HIV therapeutic agents. The research was mostly focused on the hairpin bulge site while much less is known about the apical loop region of the TAR RNA HIV-1 structure, dynamics and protein interactions.
To investigate the conformational dynamics and interactions stabilizing the structure of the apical loop in solution we have performed extensive molecular dynamics calculations of model TAR RNA hairpin. Several MD runs of the 8 ns length in explicit water box containing sodium ions with different initial structures and conditions produced dynamically stable trajectories. The 6 nucleotide loop structure is stabilized by a non canonical base interactions and stable water molecules. The dynamic stacking of guanosines at the 3? side of the loop is highly conserved within MD trajectories. Such prestacked structure may be important in respect to the RNA interactions.
This work was supported by grant from the State Committee for Scientific Research , Republic of Poland (8 T11F002 19) and VISBY Program, Swedish Institute, Sweden.
Institute of Bioorganic Chemistry