MD studies of the DIS/DIS kissing complex solution and x-ray structures

As in all retroviruses, human immunodeficiency virus (HIV) genomic RNA is packaged into virions as a dimer. The two copies of the genome are noncovalently linked by their 5'-ends in the dimerization initiating site (DIS), which folds as a hairpin containing an apical autocomplementary sequence. In vitro, DIS is able to dimerize in two conformations: a kissing complex and an extended dimer. Both conformations have been resolved by NMR and x-ray diffraction. Here, we report molecular dynamics (MD) studies of the two available structures for the DIS/DIS kissing complex in aqueous solution and in the presence of sodium counterions. The two structures behave in two different manners. On one hand, the NMR structure displays a very stable behavior, and the simulated structure remains very close to the starting structure. On the other hand, the structure issued from crystallography displays a more dynamic behavior, in which residues A8 and A9 are seen in a new and surprising bulge-in conformation. The transition from the bulge-out to the bulge-in conformation is analyzed, and a new and simple dimerization process is proposed.