Comparison of the structures of HIV-1 RT/NNRTI complexes with unliganded HIV-1 RT showng a large movement of the p66-thumb subdomain caused by the binding of an NNRTI to RT.  In the epo-enzyme structure, the p66-thumb is folded down into the DNA-binding cleft. In HIV-1 RT/NNRTI complex structures, the p66-thumb is in a hyper extended position.