Four models of DNA including A-DNA, B-DNA, Triple helix-DNA (T-DNA), and Z-DNA along with a COF molecule were prepared. Molecular dynamics simulations were performed on all DNAs and their complex with COF (embedded DNAs in the central hole of COF). Comprehensive analyses such as Base pair distance, hydrogen bonding, Van der Waals, and electrostatic interaction numbers were carried out to investigate the effect of COF molecule on DNA intermolecular interactions. Furthermore, quantum-mechanics studies were performed to explore the accuracy of intermolecular and intramolecular interactions. The results obtained based on promolecular density in two selected base pairs. Noncovalent interaction (NCI) analysis to investigate the strength of hydrogen bonds, Van der Waals interactions, and steric effect was done. Density Overlap Regions Indicator (DORI) analysis was accomplished to study the accuracy of π-π stacking interactions between adjacent bases. δg functions were evaluated to analyze the strength of chemical bonds, hydrogen bonds and also the steric effect. The average distance between O … H, N … H, and H … O that are contributing in H-bonding are ∼ 1.88, 1.97, and 1.95 Å in A-DNA, respectively. Also, the average number of H-bonding numbers in A-DNA calculated to be 14.43 and 13.04 in pure and complex form. All the achieved results showed that designed COF did not make any changes in DNA structures, but in some cases, had some effects on the interactions of DNAs.

In this study, molecular dynamics (MD) simulations were performed on cellulose and aminated cellulose. Obtained results show the presence of amine moieties and their protonation, positive charges and repulsive forces increase. As a result, the van der Waals and electrostatic interactions and hydrogen bonding number decrease. Then, paclitaxel was loaded through docking into the structures and was studied by MD simulations. The simulations were performed in several protonation states along with 25°C, 37°C, 42°C and 50°C temperatures. The carrier/ligand system behaviors were analyzed. The results indicate the increase of temperature and protonation decrease hydrogen bonding number between drug and carrier and increase binding free energy. At last, to compare the simulations results, paclitaxel was loaded in cellulose and aminated cellulose and investigated in the in vitro release at two conditions (37°C, pH 7.4, and 42°C, pH 5). Experimental results prove computational results as pH/temperature-responsive system.