Three-dimensional Quantitative Structure Activity Relationship (3D-QSAR) has been derived for a set of HEPT derivatives of HIV-1 reverse transcriptase (RT) using Comparative Molecular Field Analysis (CoMFA). The CoMFA models have been developed using two different alignment procedures such as common substructure and bioactive conformation. The CoMFA model I is derived from a common substructure procedure that includes steric and electrostatic fields with the cross-validated q(2) and the non-cross-validated r(2) value of 0.86 and 0.97, respectively. The same for the CoMFA model II that is derived based on the bioactive conformation are 0.19 and 0.77, respectively. It is evident from the results that the common substructure-based alignment model has good statistical significance when compared with that of bioactive conformation for the selected systems in this study. The docking study revealed that the conformational flexibility observed at the R3 position favors different orientations of the substitution at the active site of HIV-1 RT and thereby leads to inconsistency in the CoMFA alignment based on bioactive conformation.

3D-QSAR modeling of juvenile hormone (JH) mimetic compounds of Culex pipiens (C. pipiens) larvae were analyzed. Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) were chosen for 3D-QSAR studies. These compounds act as potential insect control agents. The dataset containing 143 JH mimetic compounds considered in this study were divided into a training set of 129 compounds and a test set of 14 compounds. The CoMFA/ CoMSIA model is obtained with the statistical significance r 2 of 0.944 (0.773) with standard error of estimate of 0.313 (0.616). Both CoMFA and CoMSIA models provide valuable insight into the structural requirements for the enhanced activity of the JH inhibitors.