Molecular docking, DFT calculation and molecular dynamics simulation of Triazine-based covalent organic framework as a nanocarrier for delivering anti-cancer drug

Covalent organic frameworks (COFs) have attracted attention as novel nanocarriers for anticancer drug delivery due to their properties such as large surface area, tunable porosity, and customizable surface capabilities. In this study, the absorption of imatinib (IMA) as an anticancer drug on a triazine-based COF was investigated through computational methods. Docking simulation was employed to identify potential binding sites and estimate the binding energy of imatinib on COF. The mean binding energy was calculated to be -6.43 kcal/mole, which is predominantly attributed to the π-π stacking interaction. Then, the most favorable complexes with good binding energies were selected for density functional theory (DFT) calculations. The calculations were performed using the ONIOM method in the presence of molecular water effects using the PCM model. The absorption energies ranged from 21.4 to 27.60 kcal/mol for the studied complex. For a deeper analysis of the interactions, natural bond orbital (NBO) analysis and quantum theory of atoms in molecules (QTAIM) were used. In addition, molecular dynamics (MD) simulations were performed to evaluate the IMA -COF complexes in aqueous environments. Based on the results, vdW interactions played an important role in the stability of the drug molecule in both inside and outside of the COF cavity. Also, the diffusion of IMA within the COF was investigated by mean square displacement (MSD) analysis which showed the restricted mobility of IMA within the COF compared to the aqueous media. The results of this study confirm the ability of COFs as drug delivery systems and suggest the targeted design of these structures according to the drug structure.