BMS-378806　is　a　newly　discovered　small　molecule　that　effectively　blocks　the　binding　of　CD4　with　gp120.　The　binding　mode　of　this　kind　of　inhibitor　remains　unknown.　In　this　paper,　AutoDock　3.0　in　conjunction　with　molecular　dynamics　simulation,　accommodating　the　receptor＇s　flexibility,　was　used　to　explore　the　binding　mode　between　BMS-378806　and　gp120.　Two　structures,　Mode　I　and　Mode　II,　with　the　lowest　docking　energy　were　selected　as　different　representative　binding　modes.　The　analysis　of　the　results　from　the　molecular　dynamics　simulation　indicated　that　the　binding　of　BMS-348806　in　Mode　II　is　more　stable.　The　average　structure　of　Mode　II　was　analyzed　and　compared　with　the　experimental　data.　The　conclusion　was　that　BMS-378806　inserts　the　azaindole　ring　deeply　into　the　PHE43　cavity　and　makes　contact　with　a　number　of　residues　in　the　cavity,　on　the　cavity　and　near　the　cavity.　This　study　benefits　the　understanding　of　the　mechanism　of　this　kind　of　inhibitor　and　may　provide　useful　information　for　rational　drug　design.　(c)　2005　Elsevier　B.V.　All　rights　reserved.