Analysis of B-Raf inhibitors using 2D and 3D-QSAR, molecular docking and pharmacophore studies

摘要

In the present work, a molecular modeling study was carried out using 2D and 3D quantitative structure-activity relationships for the various series of compounds known as B-Raf inhibitors. For 2D-QSAR analysis, a linear model was developed by MLR based on GA-OLS with appropriate results , which was validated by several external validation techniques. To perform a 3D-QSAR analysis, CoMFA and CoMSIA methods were used. The selected CoMFA model could provide reliable statistical values based on the training set in the biases of the selected alignment. Using the same selected alignment, a statistically reliable CoMSIA model, out of thirty-one different combinations, was also obtained . The predictive accuracy of the derived models was rigorously evaluated with the external test set of nineteen compounds based on several validation techniques. Molecular docking simulations and pharmacophore analyses were also performed to derive the true conformations of the most potent inhibitors with B-Raf kinase.