Analysis of B-Raf[Formula: see text] inhibitors using 2D and 3D-QSAR, molecular docking and pharmacophore studies.
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[Formula: see text] inhibitors. For 2D-QSAR analysis, a linear model was developed by MLR based on GA-OLS with appropriate results [Formula: see text], 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 [Formula: see text] 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 [Formula: see text]. 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[Formula: see text] kinase.
Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, P. O. Box 157 71, Athens, Greece.
Reza
R
Aalizadeh
Department of Chemistry, Payame Noor University, P. O. Box 19395-3697, Tehran, Iran. pourbasheer@ut.ac.ir.
Eslam
E
Pourbasheer
Center of Excellence in Electrochemistry, University of Tehran, Tehran, Iran.|Biosensor Research Center, Endocrinology & Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Reza
MR
Ganjali
D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D009154:Mutation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics*; D021281:Quantitative Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
3D-QSAR; B-Raf kinase; Drug design; Molecular docking; Pharmacophore