The　interaction　of　HIV-1　trans-activator　protein　Tat　with　its　cognate　trans-activation　response　element　(TAR)　RNA　is　critical　for　viral　transcription　and　replication.　Therefore,　it　has　long　been　considered　as　an　attractive　target　for　the　development　of　antiviral　compounds.　Recently,　the　conformationally　constrained　cyclic　peptide　mimetics　of　Tat　have　been　tested　to　be　a　promising　family　of　lead　peptides.　Here,　we　focused　on　two　representative　cyclic　peptides　termed　as　L-22　and　KP-Z-41,　both　of　which　exhibit　excellent　inhibitory　potency　against　Tat　and　TAR　interaction.　By　means　of　molecular　dynamics　simulations,　we　obtained　a　detailed　picture　of　the　interactions　between　them　and　HIV-1　TAR　RNA.　In　results,　it　is　found　that　the　binding　modes　of　the　two　cyclic　peptides　to　TAR　RNA　are　almost　identical　at　or　near　the　bulge　regions,　whereas　the　binding　interfaces　at　the　apical　loop　exhibit　large　conformational　heterogeneity.　In　addition,　it　is　revealed　that　electrostatic　interaction　energy　contributes　much　more　to　KP-Z-41　complex　formation　than　to　L-22　complex,　which　is　the　main　source　of　energy　that　results　in　a　higher　binding　affinity　of　KP-Z-41　over-22　for　TAR　RNA.　Furthermore,　we　identified　a　conserved　motif　RRK　(Arg-Arg-Lys)　that　is　shown　to　be　essential　for　specific　binding　of　this　class　of　cyclic　peptides　to　TAR　RNA.　This　work　can　provide　a　useful　insight　into　the　design　and　modification　of　cyclic　peptide　inhibitors　targeting　the　association　of　HIV-1　Tat　and　TAR　RNA.