RNAtertiary structure oftheHIVRREdomain11 containing non-Watson- Crick basepairs GG andGA: molecular modeling studies

Wehaveusedmolecular modeling techniques tomodel theRNAtertiary structure oftheviral RNAelement (referred toasdomain11ofRevresponsive element, RRE)boundbytheRevprotein ofHIV.Inthis study, theinitial three-dimensional modelwasbuilt fromits established RNAsecondary structure, including three non-Watson-Crick G:G,G:AandG:Ubasepairs. Molecular dynamics (MD)simulations wereperformed withhydrated orunhydrated sodiumions. Ourresults indicate that thenon-Watson -Crick basepairs inthe simulation withunhydrated sodiumionsandwaterare morestable thanthose withhydrated sodium ionsonly. TheRNA canmaintain itscompactdoublehelical structure throughout thecourseoftheMDsimulations withwaterandunhydrated sodiumions, although the non-Watson -Crick basepairs andtwobulge loops show much more flexibility andconformational distortion thantheclassical RNAhelical region. The distinct distortion ofthesugar-phosphate backbone significantly widens theRNAmajor groove sothat the majorgrooveisreadily accessible forhydrogen bondingby specific Rev binding. Thismodel emphasizes theimportance ofspecific hydrogen bonding inthestabilization ofthethree-dimensional structure oftheHIVRevcorebinding element, notonly between thenucleotide bases, butalsoamongthe ribose hydroxyls, phosphate anionic oxygens, base oxygens andnitrogens, andbridging watermolecules. Moreover, ourresults suggest thatsodiumionsplay anImportant role intheformation ofbasepalrs G:Gand G:AoftheRREbyamannersimilar tothearginine of theRev-RREcomplex.