Wild　type　(WT)　and　F185K　mutant　type　of　HIV-1　integrase　catalytic　domain　(INc)　were　expressed　and　purified,　and　their　solubility　and　activity　were　compared.　The　experiment　results　show　that　the　solubility　of　F185K　mutated　INc　was　dramatically　increased,　whereas　the　activity　was　reduced　to　some　extent.　Subsequently,　1　800　ps　molecular　dynamics　(MD)　simulations　for　the　WT　and　F185K　type　of　INc　in　water　were　performed.　The　MD　simulation　results　demonstrate　that　the　flexibility　of　the　catalytic　loop　region　and　the　total　mobility　of　F185K　INc　was　reduced,　which　causes　the　decrease　of　activity.　After　the　F185K　mutation,　changes　of　the　salt　bridge　network　drove　the　conformational　change　of　IN,　resulted　in　the　burying　of　some　hydrophobic　residues　and　exposure　of　some　other　hydrophilic　residues　on　the　protein　surface.　Therefore,　the　relative　hydrophilic　solvent　accessible　surface　of　INc　was　increased.　Moreover,　the　F185K　mutation　increased　the　hydrogen　number　between　the　INc　protein　and　water　molecule,　as　a　consequence,　the　protein-water　interaction　was　enhanced.　These　above　changes　contribute　to　the　solubility　increase　of　INc.　It　is　found　that　the　results　obtained　from　MD　simulation　are　in　good　agreement　with　the　experiment　data.　The　above　mentioned　results　provides　valuable　insight　for　the　understanding　of　protein　solubility　and　will　be　helpful　in　protein　engineering　for　increasing　the　solubility　of　proteins.