Blocking the Passage: C60 Geometrically Clogs K+ Channels

Matteo Calvaresi, Simone Furini, Carmen Domene Nunez, Andrea Bottoni, Francesco Zerbetto

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Classical molecular dynamics (MD) simulations combined with docking calculations, potential of mean force estimates with the umbrella sampling method, and molecular mechanic/Poisson–Boltzmann surface area (MM-PBSA) energy calculations reveal that C60 may block K+ channels with two mechanisms: a low affinity blockage from the extracellular side, and an open-channel block from the intracellular side. The presence of a low affinity binding-site at the extracellular entrance of the channel is in agreement with the experimental results showing a fast and reversible block without use-dependence, from the extracellular compartment. Our simulation protocol suggests the existence of another binding site for C60 located in the channel cavity at the intracellular entrance of the selectivity filter. The escape barrier from this binding site is ∼21 kcal/mol making the corresponding kinetic rate of the order of minutes. The analysis of the change in solvent accessible surface area upon C60 binding shows that binding at this site is governed purely by shape complementarity, and that the molecular determinants of binding are conserved in the entire family of K+ channels. The presence of this high-affinity binding site conserved among different K+ channels may have serious implications for the toxicity of carbon nanomaterials.
Original languageEnglish
Pages (from-to)4827-4834
Number of pages8
JournalACS Nano
Volume9
Issue number5
Early online date14 Apr 2015
DOIs
Publication statusPublished - 1 May 2015

Keywords

  • fullerene, K+ channels, nanotoxicity, molecular dynamics, protein nanoparticle interaction, MOLECULAR-DYNAMICS SIMULATION, CARBON-NANOTUBE HYBRIDS, POTASSIUM CHANNEL, CRYSTAL-STRUCTURE, FULLERENE DERIVATIVES, ELECTRON TOMOGRAPHY, LIPID-MEMBRANE, ION-CHANNEL, PROTEINS, WATER

Fingerprint Dive into the research topics of 'Blocking the Passage: C<sub>60</sub> Geometrically Clogs K<sup>+</sup> Channels'. Together they form a unique fingerprint.

Cite this