3D-QSAR study on a series of Bcl-2 protein inhibitors using comparative molecular field analysis

In this manuscript, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using comparative molecule field analysis (CoMFA) techniques were applied to provide the structural information of Bcl-2 inhibitors. The CoMFA model obtained from the training set were all statistically significant with the cross-validated coefficients (q(2)) of 0.568 and conventional coefficients (r(2)) of 0.991. The contribution of steric field and the electrostatic field is 0.635 and 0.365, respectively. The 3D-QSAR model was furthermore validated by a test set of 6 molecules. The predicted correlation coefficient (r(2)(pred)) on the test set is 0.582. Therefore, the 3D-QSAR models built may be used to exhibit the necessary ligand-based structural environment as well as to design novel Bcl-2 inhibitors with increasing activities.