HIV-1 envelope glycoprotein-mediated fusion is managed by the concerted coalescence of the HIV1 gp41 N- and C-helical regions, which is a product in the formation of 6-helix bundles. These two regions are considered prime targets for peptides and antibodies that inhibit HIV-1 entry. Most of HIV fusion inhibitors against gp41 are peptides derived from the helical C-terminal heptad repeat (CHR) of gp41, including a number of currently experimental drugs and T20 (Enfuvirtide, Fuzeon), the first and only gp41-targeting anti-HIV agent approved by the U.S. FDA. There are so many rational method aimed to attach a rationally designed artificial tail to the C-terminus of HIV-1 fusion inhibitors to increase their antiviral potency. Here we have a crystal structure which report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. Crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL was also available . Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36, and a hook-like structure with the longer N43. Here M. D. simulation was performed to go insight for study of C-terminal tail of Ile-Asp-Leu (IDL).
