title: Density functional and molecular docking studies towards investigating the role of single-wall carbon nanotubes as nanocarrier for loading and delivery of pyrazinamide antitubercular drug onto pncA protein.
abstract: The potential biomedical application of carbon nanotubes (CNTs) pertinent to drug delivery is highly manifested considering the remarkable electronic and structural properties exhibited by CNT. To simulate the interaction of nanomaterials with biomolecular systems, we have performed density functional calculations on the interaction of pyrazinamide (PZA) drug with functionalized single-wall CNT (fSWCNT) as a function of nanotube chirality and length using two different approaches of covalent functionalization, followed by docking simulation of fSWCNT with pncA protein. The functionalization of pristine SWCNT facilitates in enhancing the reactivity of the nanotubes and formation of such type of nanotube-drug conjugate is thermodynamically feasible. Docking studies predict the plausible binding mechanism and suggests that PZA loaded fSWCNT facilitates in the target specific binding of PZA within the protein following a lock and key mechanism. Interestingly, no major structural deformation in the protein was observed after binding with CNT and the interaction between ligand and receptor is mainly hydrophobic in nature. We anticipate that these findings may provide new routes towards the drug delivery mechanism by CNTs with long term practical implications in tuberculosis chemotherapy.
authors: Department of Chemical Sciences, Tezpur University, Tezpur, Assam, India.
authors: Nabanita
authors: N
authors: Saikia
authors: Sanchaita
authors: S
authors: Rajkhowa
authors: Ramesh C
authors: RC
authors: Deka
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry / Q000378:metabolism*; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011487:Protein Conformation; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D004337:Drug Carriers; D037742:Nanotubes, Carbon; D011718:Pyrazinamide; D000581:Amidohydrolases; C487496:PncA protein, Mycobacterium tuberculosis