3D-QSAR Studies on DATAs and DAPYs for HIV-RT Inhibitors using CoMFA and CoMSIA Approaches

Structure-based Quantitative Structure-Activity Relationship (QSAR) studies were performed on the Human Immunodeficiency Virus Reverse Transcriptase (HIV-RT) inhibitors with Diaryltriazines (DATAs) and Diarylpyrimidines (DAPYs) using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) implemented in the SYBYL software packages. From the Xray structure of dapivirine, 38 training set molecules were sketched and minimized using the MMFF94 force field. In structure-based QSAR, all the HIV-RT complexes were subjected to subset minimization and aligned against a fixed point of the enzyme. The best CoMFA and CoMSIA results presented cross-validated values (q(2)) of 0.640 and 0.663, and non-cross-validated values (r(2)) of 0.976 and 0.932, respectively. Contour map analysis enables the identification of crucial interactions between the enzyme and inhibitors, which can be used further to design new HIV-RT inhibitors.