In this study, 48 inhibitors were docked to 107 allosteric centers of human immunodeficiency virus 1 (HIV-1) reverse transcriptase from the Protein Data Bank (PDB). Based on the average binding scores, quantitative structure-activity relationship (QSAR) equations were constructed in order to elucidate directions of further development in the design of inhibitors. Such developments, informed by structural data, must have a focus on activity against mutated forms of the enzyme, which are the cause of the emergence of multidrug-resistant viral strains. Docking studies employed the HYDE scoring function. Two types of QSARs have been considered: One based on topological descriptors and the other on structural fragments of the inhibitors. Both methods gave similar results, indicating substructures favoring binding to mutated forms of the enzyme.
Keywords: HIV-1 reverse transcriptase; HYDE; QSAR; docking.