Investigation into the extension of the non-nucleoside reverse transcriptase binding pocket

Superimposition of 125 non-nucleoside inhibitors from human immunodeficiency virus reverse transcriptase structures reveals a novel binding space deeper into the enzyme for some of these inhibitors, allowing access to the polymerase active site. This may enable us to design new inhibitors of this enzyme with better mutation resistance profiles. We have analysed this new binding space and have docked our in-house scaffolds into this region, highlighting the possibility of the formation of new hydrogen bonds with residues of the active site. © 2011 CSIRO.