Simulation of polymer translocation through protein channels

Abstract

A modeling algorithm is presented to compute simultaneously polymer conformations and ionic current, as single polymer molecules undergo translocation through protein channels. The method is based on a combination of Langevin dynamics for coarse-grained models of polymers and the Poisson-Nernst-Planck formalism for ionic current. For the illustrative example of ssDNA passing through the alpha-hemolysin pore, vivid details of conformational fluctuations of the polymer inside the vestibule and beta-barrel compartments of the protein pore, and their consequent effects on the translocation time and extent of blocked ionic current are presented. In addition to yielding insights into several experimentally reported puzzles, our simulations offer experimental strategies to sequence polymers more efficiently.

Fig. 1.

United atom model. (a) The end and side views of αHL. The diameters at the center and mouth of the vestibule are 46 and 30 Å, respectively. (b) The internal wall of the nanotube is made of spherical beads on a curved hexagonal lattice. The interaction between polymer and tube is taken as the Lennard–Jones potential of Eq. 5 with ε = 0.2 kcal/mol and σ = 2.75 Å. (c) United atom representation of single-stranded poly(dC).

Fig. 2.

PNP and approximated V(X) across the protein pore.

Fig. 3.

Typical ionic current traces. (A) Long τ. (B) Short τ.

Fig. 4.

Histogram of τ for αHL (n = 45, V₀ = 120 mV).

Fig. 5.

Histogram of I_b. A and B correspond, respectively, to Fig. 3 A and B.

Fig. 6.

Typical ionic current trace for a nanotube.

Fig. 7.

Comparison of P(τ) between αHL and nanotube.

Fig. 8.

Proposed experiment. (A) Strategy. (B and C) The ionic current traces for two homopolymers (B) and two heteropolymers (C) (sequence given in Inset). Each polymer has eight bases.