Assessment of Nonnucleoside Inhibitors Binding to HIV-1 Reverse Transcriptase Using HYDE Scoring
Faculty of Pharmacy with Medical Analytics Division, Medical University of Lublin, Chodźki 4a, 20-093, Lublin, Poland
FQS-Fujitsu Poland, Parkowa 11, 33-332 Kraków, Poland
Institute of Applied Radiation Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(2), 64; https://doi.org/10.3390/ph12020064
Received: 1 April 2019 / Revised: 19 April 2019 / Accepted: 20 April 2019 / Published: 24 April 2019
(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs)
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.