Correlation weighted successive projections algorithm as a novel method for variable selection in QSAR studies: investigation of anti‐HIV activity of HEPT derivatives

Abstract

Correlation weighted successive projections algorithm (CWSPA), as a modified version of successive projections algorithm (SPA), is proposed for selection of descriptors in the non-linear quantitative structure-activity relationship (QSAR) study of a series of 1-[2-hydroxyethoxy-methyl]-6-(phenylthio)thymine] (HEPT) derivatives, as non-nucloside reverse transcriptase inhibitors (NNRTIs). In the proposed procedure the correlation coefficient of each descriptor with the activities (r g ) was an additional criterion for selection of descriptors. The extent of contribution of r in the selection of variables, m, was also optimized and r 4 g -CWSPA was the selected condition (m ¼ 4). Three layer radial basis function networks (RBFNs) and molecular descriptors derived solely from molecular structure were used to construct the non-linear QSAR models. Utilizing r 4 g -CWSPA a limited number of uncorrelated and informative descriptors were selected. The relative standard error percent in anti-HIV activity predictions for the training set by the application of cross-validation (RSECV%) was 9.77%, and for prediction set (RSEP%) was 8.61% when the selected number of descriptors were 20. The obtained model outperforms those given in the literature in both the fitting and predicting stages. RBFN analysis yielded predicted activities in an acceptable agreement with the experimentally obtained values (cross-validation r ¼ 0.924, prediction r ¼ 0.939). Compared to SPA, r m g -CWSPA resulted in a lower RSECV% and RSEP% values using lower number of selected variables. The results show that considering the correlation of variables to the independent variables increase the performance of selection, as a result, the quality of the set of selected variables. Finally, a simple procedure for selection of variables using r 4 g -CWSPA was proposed in which there was no need to test all possible initial descriptors. The results from the simple procedure were comparable to the procedure in which all of the possible initial descriptors were tested. The proposed method was successfully validated by five different training and test sets.

Quantitative Structure–Activity Relationship Study on the Anti‐HIV‐1 Activity of Novel 6‐Naphthylthio HEPT Analogs

“…In summary, it is concluded that electronegativity, the masses, and the atomic van der Waals volumes play a main role in the anti‐HIV‐1 activity of the studied compounds. These results agree with recently published papers (48,49).…”

Chemometrics tools in QSAR/QSPR studies: A historical perspective

“…Because of the good potential of SPA, this algorithm has been utilized efficiently in descriptor selection of QSAR/QSPRs and in some cases with few modifications and hyphenation [126][127][128][129][130][131][132][133][134][135][136][137][138][139].…”

A perspective on the growth of chemometrics in Iran: a glance into activities between 2005 and 2012

“…Proposing new methods for variable selection in QSAR studies is an interesting topic for Iranian chemometrician. Kompany‐Zareh and Akhlaghi proposed the correlation weighted successive projections algorithm as a novel method for variable selection in QSAR studies . They used this method to investigate anti‐HIV activity of HEPT derivatives.…”