Integrase　is　an　essential　enzyme　in　the　life　cycle　of　Human　immunodeficiency　virus　type　I　(HIV-1)　and　also　an　important　target　for　designing　integrase　inhibitors.　In　this　paper,　the　binding　modes　between　the　wild　type　integrase　core　domain　(ICD)　and　the　W131A　mutant　ICD　with　the　benzoic　acid　derivative　-　D77　were　investigated　using　the　molecular　docking　combined　with　molecular　dynamics　(MD)　simulations.　The　result　of　MD　simulations　showed　that　the　W131A　substitution　affected　the　flexibility　of　the　region　150-167　in　both　the　monomer　A　and　B　of　the　mutant　type　ICD.　In　principle,　D77　interacted　with　the　residues　around　the　Lens　Epithelium-Derived　Growth　Factor　(LEDGF/p75)　binding　site　which　is　nearby　the　HIV-1　integrase　dimer　interface.　However,　the　specific　binding　modes　for　D77-wild　type　integrase　and　D77-mutant　integrase　systems　are　various.　According　to　the　binding　mode　of　D77　with　the　wild　type　ICD,　D77　can　effectively　intervene　with　the　binding　of　LEDGF/p75　to　integrase　due　to　a　steric　hindrance　effect　around　the　LEDGF/p75　binding　site.　In　addition,　we　found　that　D77　might　also　affect　its　inhibitory　action　by　reducing　the　flexibility　of　the　region　150-167　of　integrase.　Through　energy　decomposition　calculated　with　the　Molecular　Mechanics　Generalized　Born　Surface　Area　approach　to　estimate　the　binding　affinity,　it　seems　likely　that　W131　and　E170　are　indispensable　for　the　ligand　binding,　as　characterized　by　the　largest　binding　affinity.　All　the　above　results　are　consistent　with　the　experimental　data,　providing　us　with　some　helpful　information　not　only　for　the　understanding　of　the　mechanism　of　this　kind　of　inhibitor　but　also　for　the　rational　drug　design.