Book of Abstracts: Albany 2003
June 17-21 2003
Conformational Dynamics of HIV-1 Adenosine Rich Loop
HIV-1 adenosine-rich (A-rich) loop mediate complex formation between viral RNA and cellular tRNA. The NMR study showed that the A-rich loop is stabilized by sheared G:A base pair and a U-turn motif.
Dynamic behavior of A-rich loop has been investigated by the means of molecular dynamics simulation (MD) in the presence of counterions and explicit water molecules. MD simulation was performed on the GGUGUAAAAAUC nucleotide fragment corresponding to the nucleotides 159-170 of the A-rich loop from HIV-1 Mal isolate, starting from the NMR structure.
Results of 7.5 ns long MD simulation suggested that A-rich loop is more flexible as have been inferred from NMR studies. The stem region (nucleotides G159-U161 and A168-C170) stayed close to the initial structure but displayed reversible distortion events. In the G160:U169 wobble base pair O6...H3 hydrogen bond from the major groove was mediated by a water molecule. The sheared G162:A167 base pairs appeared to be the most stable motif of the structure. The A164-A166 bases of the loop nucleotides 3? to the U-turn showed large variation in orientation. They were found in the orientation parallel and also nearly perpendicular to the sheared G162:A167 base pairs. The sugar of A164 changed the conformation from C3?-endo to the C2?-endo. Particular interactions thought to stabilize the U-turn were not maintained during the course of entire simulation time but general loop shape was preserved. Structural changes which took place during simulation made loop bases more accessible to the solvent.
This work was supported by KBN grant 8 T11F002 19, Poland, and Visby Program, Swedish Institute, Sweden.
Institute of Bioorganic Chemistry