Human　immunodeficiency　virus　type　1　(HIV-1)　integrase　(IN)　is　an　essential　enzyme　in　the　lifecycle　of　this　virus　and　also　an　important　target　for　the　study　of　anti-HIV　drugs.　The　binding　mode　of　the　wild　type　IN　core　domain　and　its　G140S　mutant　with　L-Chicoric　acid　(LCA)　inhibitor　were　investigated　by　using　multiple　conformation　molecular　docking　and　molecular　dynamics　(MD)　simulation.　Based　on　the　binding　modes,　the　drug　resistance　mechanism　was　explored　for　the　G140S　mutant　of　IN　with　LCA.　The　results　indicate　that　the　binding　site　of　the　G140S　mutant　of　IN　core　domain　with　LCA　is　different　from　that　of　the　core　domain　of　the　wild　type　IN,　which　leads　to　the　partial　loss　of　inhibition　potency　of　LCA.　The　flexibility　of　the　IN　functional　loop　region　and　the　interactions　between　Mg2+　ion　and　the　three　key　residues　(Le.,　D64,　D116,　E152)　stimulate　the　biological　operation　of　IN.　The　drug　resistance　also　lies　in　several　other　important　effects,　such　as　the　repulsion　between　LCA　and　El　52　in　the　G140S　mutant　core　domain,　the　weakening　of　K159　binding　with　LCA　and　Y143　pointing　to　the　pocket　of　the　G140S　mutant.　All　of　the　above　simulation　results　agree　well　with　experimental　data,　which　provide　us　with　some　helpful　information　for　designing　the　drug　of　anti-HIV　based　on　the　structure　of　IN.