Conformational transitions of flanking purines in HIV‐1 RNA dimerization initiation site kissing complexes studied by CHARMM explicit solvent molecular dynamics

Dimerization of HIV‐1 genomic RNA is initiated by kissing loop interactions at the Dimerization Initiation Site (DIS). Dynamics of purines that flank the 5′ ends of the loop–loop helix in HIV‐1 DIS kissing complex were explored using explicit solvent molecular dynamics (MD) simulations with the CHARMM force field. Multiple MD simulations (200 ns in total) of X‐ray structures for HIV‐1 DIS Subtypes A, B, and F revealed conformational variability of flanking purines. In particular, the flanking purines, which in the starting X‐ray structures are bulged‐out and stack in pairs, formed a consecutive stack of four bulged‐out adenines at the beginning of several simulations. This conformation is seen in the crystal structure of DIS Subtype F with no interference from crystal packing, and was frequently reported in our preceding MD studies performed with the AMBER force field. However, as CHARMM simulations progressed, the four continuously stacked adenines showed conformational transitions from the bulged‐out into the bulged‐in geometries. Although such an arrangement has not been seen in any X‐ray structure, it has been suggested by a recent NMR investigation. In CHARMM simulations, in the longer time scale, the flanking purines display the tendency to move to bulged‐in conformations. This is in contrast with the AMBER simulations, which indicate a modest prevalence for bulged‐out flanking base positions in line with the X‐ray data. The simulations also suggest that the intermolecular stacking between purines from the opposite hairpins can additionally stabilize the kissing complex. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 732–746, 2008.