The role of salt concentration and magnesium binding in HIV-1 subtype-A and subtype-B kissing loop monomer structures

The subtype-B monomers of the human immunodeficiency virus type-1 (HIV-1) have experimentally been shown to dimerize at high salt concentration or in the presence of magnesium, while the dimerization of the subtype-A monomers requires magnesium binding at the G273 or G274 phosphate groups regardless of salt concentration. We used explicit solvent molecular dynamics (MD) simulations to investigate the conformational changes in subtype-A and -B monomers in different salt concentrations, and we found that our MD simulation results are consistent with those of experiments. At low salt concentration, hairpin loop structures of both subtypes were deformed and bases in the hairpin loop were turned inside. At high salt concentrations, the subtype-B monomer maintained the hairpin loop shape and most bases in the hairpin loop pointed out, while the subtype-A monomer showed a severe deformation. We also found that the flanking bases in the subtype-B stabilize the hairpin loop, while the flanking base G273 in the subtype-A caused a significant deformation. However, a bound magnesium ion at the G273 or G274 phosphate groups controlled the behavior of the G273 base and prevented the subtype-A monomer from deformation. We also applied restraints to both subtypes to examine the role of high salt concentration or magnesium binding. While restraints were applied, both subtypes at 0 M salt concentration maintained their shapes. However, when restraints were removed, they deformed significantly. Therefore, we suggest that the dimerization of both subtypes requires the proper conformation of the monomers which is induced by the appropriate salt strength and magnesium ion binding.