ADVANCED COMPUTATIONAL DOCKING OF 2 TELEOCIDIN CONGENERS TO CYS2 DOMAIN OF PROTEIN-KINASE C-DELTA

We simulated the docking of two teleocidin congeners to the cys2 domai n structure observed in the crystalline complex of protein kinase C de lta with phorbol-13-acetate. The most stable docking models were searc hed for two conformers of (-)-indolactam-V ((-)-IL-V), twist and sofa form, and for (-)-benzolactam-V ((-)-BL-V8) by using an automatic dock ing method, ADAM, which can cover all possible binding modes and confo rmations. The twist form of (-)-IL-V and (-)-BL-V8 molecules fitted we ll into the same cavity as phorbol-13-acetate, Of the three functional groups hydrogen-bonding to the protein, two hydrogen-bonded with prot ein atoms in common with phorbol-13-acetate, but the third one hydroge n-bonded with a different protein atom from that in the case of phorbo l-13-acetate.