The Investigation of inhibitory effect of Isocochliodinol on HTLV-1 and HIV Protease by molecular docking simulations

Isocochliodinol is a secondary fungal metabolite that inhibits HIV protease. HIV and HTLV-1 protease are the members of aspartic acid protease family that play important roles in the virus replication and maturation cycle. Sequence alignment results showed that HTLV-1 Protease and HIV Protease are similar more than 28%. In this work, inhibitory effect of Isocochliodinol on HTLV-1 Protease and HIV protease was investigated by molecular docking simulations. At first, 3D models of HIV and HTLV-1 protease (PDB code: 1YT9 and 3LIN) was optimized by Gromacs. To predict ligand-protein binding mode, Focused and Blind Docking were performed by Autodock. Based on focused docking results, Isocochliodinol respectively inhibit HTLV-1 Protease and HIV Protease with inhibition constant 50.49 nM and 698.32 nM. Blind docking results showed that HTLV-1 Protease and HIV Protease inhibited by Isocochliodinol with inhibition constants 4.12 nM and 4.92 nM, respectively. Isocochliodinol connected to HTLV-1 Protease via two hydrogen bonds (Ile3, Val112) and HIV Protease via one hydrogen bond (Pro1). It is concluded that Isocochliodinol potentially is able to inhibit HTLV-1 protease by connecting to a new subpocket outside of protease active site.

کلیدواژه ها:

HTLV ، 1 Protease ، HIV Protease ، Isocochliodinol ، molecular docking simulations