The present study deals with the estimation of the anti-HIV activity of a large set of 107 HEPT analogues using molecular descriptors which are responsible for the anti-HIV activity. The study has been undertaken by three techniques MLR, ANN, and SVM. The MLR model fits the train set with while in ANN and SVM with higher values of , respectively. SVM model shows improvement to estimate the anti-HIV activity of trained data, while in test set ANN have higher value than those of MLR and SVM techniques. metrics and ridge regression analysis indicated that the proposed four-variable model MATS5e, RDF080u, T(O？O), and MATS5m as correlating descriptors is the best for estimating the anti-HIV activity (log 1/C) present set of compounds. 1. Introduction Undoubtedly Human immunodeficiency virus (HIV) infection is considered to be a deadly disease by the international community including the World Health Organization (WHO), UNAIDS. The WHO in its reports has said that AIDS has killed more than 25 million people since 1981 which is most the destructive pandemics in the history. It is also a well-known fact that a lentivirus (a member of the retrovirus family) causes acquired immunodeficiency syndrome (AIDS) [1, 2], damaging immune system and leading to life-threatening infections. A report published in 2007 reveals that approximately 36 million people suffered due to HIV infection. An estimated 2.1 million people were even killed that year including 330,000 children. Another study also reveals that 2.5 million people developed new infections [3–6]. Unfortunately the number of deaths is still rising due to this deadly disease. Just to overcome the problem scientists are working day and night and a number of RT inhibitors including various nonnucleoside RT inhibitors (NNRTIs) have been discovered as new anti-HIV agents. They have better blocking potential and have been proved to be effective [7–9]. These compounds 1-[2-Hydroxyethoxy) methyl]-6-(phenylthio)-thymine (HEPT) are known for targeting enzyme allosteric site which are less toxic and found to have more stable than nucleoside RT inhibitors. Many efforts have been made to model the anti-HIV activity of HEPT derivatives in the past using 2D, 3D, and holographic (HQSAR) methods [10–13]. Quantitative structure activity relationship studies were carried out in order to build models for the estimation of binding affinities ( ) of HEPT and nevirapine analogues with reverse transcriptase [14]. Similarly, Agrawal et al. [15, 16] have successfully reported use of physicochemical as well as topological indices for
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