Molecular dynamics (MD) simulations were used to refine and extend a theoretical model that describes the interactions of single polyethylene glycol molecules (PEGs) with an α-hemolysin nanopore. A previously developed analytical model assumed that PEG decreases the conductance of the pore by volume exclusion and by binding cations (which reduces the number of mobile ions in the pore). MD simulations quantify the essential physical properties such as the average PEG geometry and PEG-cation complexes. The simulations show that although four monomers coordinate a single cation in a crown-ether like structure, on average, only 1.5 ions are bound per PEG 29-mer when the bulk electrolyte concentration is relatively high (4 M KCl). Two key experimental quantities of PEG are quantitatively described by the model: the ratio of single channel current in the presence of PEG to that in the polymers absence (blockade depth), and the mean residence time of PEG in the pore. The refined theoretical model is simultaneously fit to the experimentally determined current blockade depth and the mean residence times for PEGs with different sizes, applied transmembrane potential, and for three electrolyte concentrations. The model estimates the free energy of the PEG- cation complexes to be -5.3 kBT. Finally the entropic penalty of confining PEG to the pore is inversely proportional to the electrolyte concentration, which is consistent with polymer theory.
Citation: Journal of the American Chemical Society
Pub Type: Journals
Molecular dynamics, nanopore, alpha-hemolysin, PEG, DNA sequencing