Docking of non-nucleoside inhibitors: neotripterifordin and its derivatives to HIV-1 reverse transcriptase.

The docking of small molecules to proteins has played an important role in the understanding of drug/receptor interactions. An important drug/receptor interaction is between non-nucleoside inhibitors of HIV-1 RT and the non-nucleoside binding pocket. We report the results of docking calculations in which we have docked known and proposed non-nucleoside reverse transcriptase inhibitors to the type 1 virus. The proposed NNRTIs dock in a similar position and orientation as known inhibitors. In addition, we observe a linear correlation between the calculated interaction energy and EC50 for the inhibitors, suggesting that the docked structure orientation and the interaction energies are reasonable. Two hydrogen bonds between nevirapine and RT (3HVT and 1VRT) are observed and are reproduced across different docking schemes. Since we used two different HIV-1 RT crystal structures (3HVT and 1VRT), which are at different levels of resolution (2.9 and 2.2 A, respectively), we propose that structures with resolutions better than 3 A can be used to produce reasonable docking results. Copyright 2002 Wiley-Liss, Inc.