Interactions of G-quadruplex DNA binding site with berberine derivatives and construct a structure-based QSAR using docking descriptors

The G-quadruplex DNA has been suggested as a potential target for anticancer drugs. In this work, molecular dynamics simulation was performed on four-stranded G-quadruplex with the sequence d(TTAGGG)₄ to obtain its conformation in a water environment. Docking analysis between the most potent inhibitor and final conformation of G-quadruplex showed that there are hydrophobic interactions between inhibitors with the nucleotides of G3, G8, G9, G10, G15, G16, G21, G22, and T17, π–π stacking interaction with G-quartet and hydrogen bond interaction with sugar oxygen atom of G10 with 3.19 Å length. The types of interactions were in agreement with the results of radius of gyration values calculated for G-quadruplex (1.27 ± 0.02) and complex (1.27 ± 0.04), indicating that the DNA conformation did not change in complex formation. Docking studies were confirmed using re-docking of reported complexes by X-ray crystallography. The LS-SVR model was constructed from the descriptors created from docking and molecular structures with correlation coefficient (R = 0.905) and leave-one-out cross-validated R ² (LOO Q ² = 0.804). Also, the values of coefficient of determination and RMSE for prediction set were found to be 0.819 and 0.147, respectively. The constructed model has potential to be applied for predicting activity of new inhibitors.