View of the non-nucleoside inhibitor binding pocket (NNIBP) region from its putative entrance in HIV-1 RT/ds DNA structure. In absence of a bound inhibitor, the NNIBP is occupied with the side-chains of Tyr181 and Tyr188. However, there is a surface depression at the entrance of the NNIBP, marked by a green star in the picture.

Comparison of the structures of HIV-1 RT complexed with 1st. generation NNRTIs (8-Cl TIBO, alpha-APA, and nevirapine) revels a common mode of, "a butterfly like", nonnucleoside inhibitor (NNRTI) binding to the enzyme. However, our recent structures of HIV-1 RT with new Janssen NNRTIs have shown diverging modes (not shown in this picture) of NNRTI binding which are very different from the shown butterfly mode. These variations in NNRTI binding modes are helpful in designing improved NNRTIs.