Density functional study on noncovalent functionalization of pyrazinamide chemotherapeutic with graphene and its prototypes

We perform density functional studies to comprehend the structure and energetics of the interaction of the drug pyrazinamide (PZA) with graphene-based nanomaterials using a noncovalent functionalization approach, followed by molecular docking on the PZA-nanosheet system with the pncA protein. The structural deformation within the nanosheet induced by adsorbed PZA, adsorption energies and global reactivity descriptors are compared for the studied systems at all probable adsorption sites. Significant crumpling of the nanosheets is observed upon adsorption of PZA, with the effect being more pronounced for defect modified, BN and Stone-Wales (SW) defect nanosheets. The inclusion of dispersion corrected DFT (DFT-D) calculations takes into account the weak noncovalent van der Waals pi-pi stacking and the variation of adsorption energy, energy gap and dipole moment are compared with the results of DFT-GGA. Docking studies help in predicting the plausible binding mechanism between nanosheet-PZA systems and pncA protein and suggests that PZA loaded onto the nanomaterials facilitates the target binding of the drug within the protein. Interestingly, presence of nanosheets does not induce any major structural deformation in the protein, with the interaction between ligand and receptor being mainly hydrophobic in nature, and the doped nanosheets are found to be better docked compared to perfect sheets.