34 novel ATR inhibitors were used to build an optimal 3D-QSAR model. Homology modeling and molecular docking were used to study the interaction of ATR kinase protein and inhibitor. The results showed that both the CoMFA model (q2 = 0.550; r2 = 0.978; standard error of estimate [SEE] = 0.129; F = 177.729 and r2pred = 0.530) and the CoMSIA model (q2 = 0.632; r2 = 0.991; standard error of estimate [SEE] = 0.088; F = 277.224 and r2 pred = 0.322) are acceptable. The 3D-model of ATR kinase was further assessed by ERRAT, WHATCHECK and PROCHECK, which showed that the final model is reliable with 78.9% of the residues in the most favored regions. According to molecular docking, Ala562, Ser563, Leu564 and Lys585 were the vital amino acid residues to the ATR kinase. This article can support useful information for designing novel and high bioactive ATR kinase inhibitors.
Keywords: ATR inhibitor, 3D-QSAR, CoMFA, CoMSIA, Homology modeling, Molecular docking.