Human　immunodeficiency　virus　type　1.　(HIV-1)　integrase　(IN),　which　aids　the　integration　of　viral　DNA　into　the　host　chromosome,　is　an　essential　enzyme　in　the　lifecycle　of　this　virus　and　also　an　important　target　for　the　study　of　anti-HIV　drugs.　Recently　synthesized　12-mer　EBR28　which　was　identified　through　the　yeast　two-hybrid　system　and　could　strongly　bind　to　IN　is　one　of　the　most　potential　small　peptide　leading　compounds　inhibiting　IN　binding　to　viral　DNA.　The　binding　mode　of　IN　core　domain　and　its　peptide　inhibitor　EBR28　was　investigated　by　using　molecular　docking　and　molecular　dynamics　(MD)　simulation　and　confirmed　with　a　semi-empirical　binding　free　energy　calculation　method,　i.e.　MM-GBSA　model.　The　results　show　that　EBR28　binds　to　the　interspace　between　alpha　1　helix　and　alpha　5　helix　in　the　IN　core　domain　mainly　through　hydrophobic　interactions,　which　impedes　the　dimerization　of　the　two　IN　monomers　and　inhibits　IN　binding　to　viral　DNA　in　the　end.　The　correlation　between　calculated　and　experimental　binding　free　energies　is　very　good　(r=0.88).　All　of　the　above　simulation　results　agree　well　with　experimental　data,　which　provide　us　with　some　helpful　information　for　designing　anti-HIV　small　peptide　drugs　based　on　the　structure　of　IN.