Abstract

Tetrahydro-imidazo[4,5,l-jk][1,4]-benzodiazepin-2 (1 H)one (TIBO) is a noncompetitive non nucleotide antiretroviral drug with a specific allosteric binding site of HIV-1 RT. The conformational analysis shows that the effect of the drug depends on the potential energy which varied due to the beta rotatable dihedral angles (N6 - C15 - C16 = C17) of the TIBO side chain. The change of binding energy between TIBO and HIV-RT due to the variation in beta rotatable dihedral angles was determined. The theoretical simulation for a step size of 30 degrees variation from 0 to 90 degree changes was performed. The derived binding energies range from 0 to 8 kcal/mol. Changes in the beta dihedral angle conformation critically affects the binding energy. TIBO derivatives that affect the beta angle can change the binding energy between drug and HIV-RT and this can affect drug activity.

Key words: TIBO, HIV-RT, angle.