Consensus features of CP-MLR and GA in modeling HIV-1 RT inhibitory activity of 4-benzyl/benzoylpyridin-2-one analogues.

摘要

The HIV-1 reverse transcriptase (RT) inhibitory activity of benzyl/benzoylpyridinones is modeled with molecular features identified in combinatorial protocol in multiple linear regression (CP-MLR) and genetic algorithm (GA). Among the features, nDB and LogP are found to be the most influential descriptors to modulate the activity. Although the coefficient of nDB suggested in favor of benzylpyridinones skeleton, the coefficient of LogP suggested the favorability of hydrophilic nature in compounds for better activity. The partial least squares analysis of the descriptors common to CP-MLR and GA has displayed their predictivity over the total descriptors identified in both the approaches. The back-propagation artificial neural networks model from the five most significant common descriptors (nDB, T(O..O), MATS8e, LogP, and BELp4) has explained 93.2% variance in the HIV-1 RT activity of the training set compounds and showed a test set r(2) of 0.89. The results suggest that the descriptors have the ability to identify the patterns in the compounds to predict potential analogues.