Human immunodeficiency virus protease (HIV-1PR) is an emerging and potential drug target for anti-HIV therapy. This enzyme plays a crucial role in the process of viral maturation and infectivity. Increased resistance in strains of protease inhibitors is a major obstacle to anti-HIV therapy. The aim of the study was to correlate the chemical structure of compounds with experimental data from biological activity anti-HIV-1 protease. In the present study a series of 5,6-dihydro-2-pyrones derivatives (containing 24 compounds) as HIV-1PR inhibitors was subjected to quantitative structure–activity relationship (QSAR) analysis. For building the regression models, genetic function approximation (GFA) were used to predict the HIV-1PR inhibition activity. Based on prediction, the best validation model for anti-HIV inhibition activity with squared correlation coefficient (R2)= 0.9541, cross validated correlation coefficient (Q2cv)= 0.7440 and external prediction ability pred_R2= 0.9266 showed that Sum of E-State descriptors of strength for potential Hydrogen Bonds of path length 6, Minimum E-State descriptors of strength for potential Hydrogen Bonds of path length 6, Overall or summation solute hydrogen bond basicity and Solvation Energy were the positive contributors. Leave one out cross validation and Y-randomization analysis were performed in order to confirm the robustness of the model. The proposed model provides a better understanding on the binding mode pattern of the compounds to the binding site of HIV-1 enzyme. The results of the present study is useful for designing more potent HIV-1PR inhibitors.
