Blocking　HIV-1　viral　entry　into　the　host　cell　offers　a　promising　new　strategy　for　interfering　with　the　HIV-1　life　cycle.　A　major　target　of　inhibitor　design　is　to　prevent　the　binding　of　gp41　C-terminal　region　to　the　trimeric　coiled　coil　of　fusion-active　N-terminal　region.　We　report　here　2　ns　molecular　dynamics　(MD)　simulation　results　on　14-residue　C-peptides　(C14wt　and　C14link)　which　derived　from　the　C-terminal　region　and　complexes　of　C-peptides　and　N-terminal　region.　Both　peptides　were　docked　manually　to　the　hydrophobic　pocket　of　gp41　based　on　the　structural　information　of　N-terminal　using　AUTODOCK　3.0.　The　MD　simulations　were　carried　out　in　water　using　GROMACs　3.0.　The　interaction　energies　were　calculated　with　the　linear　interaction　energy　method　developed　by　Aqvist　et　al.　The　analysis　results　show　that　there　is　a　relationship　between　the　inhibitory　potency　and　the　stability　of　corresponding　helix.　Three　residues　(Trp628,　Glu630　and　Ile635)　from　the　C14wt　insert　into　the　hydrophobic　pocket　of　gp41　and　make　extensive　hydrophobic　contacts.　Four　residues　(Trp628,　Gln629,　Asp632,　and　Gln636)　from　the　C14link　are　deeply　buried　in　the　hydrophobic　pocket　of　gp41　and　make　extensive　hydrophobic　contacts.　Results　provide　strong　evidence　that　the　use　of　the　crosslinker　can　improve　the　helix　stabilization　and　the　inhibitory　potency.　(C)　2004　Elsevier　B.V.　All　rights　reserved.