Open Access Article

Title: Multidrug resistance protein P-gp interaction with nanoparticles (fullerenes and carbon nanotube) to assess their drug delivery potential: a theoretical molecular docking study

Authors: Sergey Shityakov; Carola Förster

Addresses: Department of Anesthesiology and Critical Care, University of Würzburg, 97080 Würzburg, Germany ' Department of Anesthesiology and Critical Care, University of Würzburg, 97080 Würzburg, Germany

Abstract: P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain chemical balance in mammalian cells for endogenous and exogenous chemical compounds. However, despite the extensive characterisation of P-gp potential interaction with drug-like molecules, the interaction of carbon nanoparticles with this type of protein molecule is poorly understood. Thus, carbon nanoparticles were analysed, such as buckminsterfullerenes (C20, C60, C70), capped armchair single-walled carbon nanotube (SWCNT or C168), and P-gp interactions using different molecular docking techniques, such as gradient optimisation algorithm (ADVina), Lamarckian genetic algorithm (FastDock), and shape-based approach (PatchDock) to estimate the binding affinities between these structures. The theoretical results represented in this work show that fullerenes might be P-gp binders because of low levels of Gibbs free energy of binding (ΔG) and potential of mean force (PMF) values. Furthermore, the SWCNT binding is energetically unfavourable, leading to a total decrease in binding affinity by elevation of the residual area (Ares), which also affects the π-π stacking mechanisms. Further, the obtained data could potentially call experimental studies using carbon nanostructures, such as SWCNT for development of drug delivery vehicles, to administer and assess drug-like chemical compounds to the target cells since organisms probably did not develop molecular sensing elements to detect these types of carbon molecules.

Keywords: P-glycoprotein; carbon nanoparticles; fullerenes; single-walled carbon nanotubes; SWCNT; CNTs; molecular docking; Gibbs free energy of binding; mean force potential; pi-pi stacking; multidrug resistance; drug delivery; gradient optimisation; Lamarckian genetic algorithms; shape-based approach.

DOI: 10.1504/IJCBDD.2013.056801

International Journal of Computational Biology and Drug Design, 2013 Vol.6 No.4, pp.343 - 357

Available online: 27 Aug 2013 *