Chemistry Reference
In-Depth Information
pores plays a major role in biological processes and also has a large potential for
technological applications. Molecular transport is indeed one of the key functions
fulfilled by the plasma and membranes of the cell, and a sizable amount of transport
mechanisms which work in the cell are characterized by the same general design,
namely by the presence of pores, mostly through membrane proteins. The con-
trolled transport of single molecules through synthetic or biological nanopores is
considered as a versatile tool of single molecule sensing and to be a most promising
candidate for rapid DNA sequencing.
The complex interplay of interactions - electrostatic, hydrodynamic, and
specific chemical ones - and the entropic properties of chain molecules make a
full understanding of these systems very difficult. The presence of an interface
between the highly polarizable aqueous solution (
e
80) and the membrane which
is much less polarizable (
e
2) leads to repelling forces between charged objects
and the pore wall. Since DNA is a highly charged molecule this effect is likely not
to be negligible and potentially gives rise to an energetic barrier that that the DNA
has to overcome in order to tranverse the pore. Its characteristics and dependence on
the pore size, DNA length, or salt concentration are not known.
The role of the dielectric mismatch between solvent and pore can be investigated
via a simple model DNA, consisting of a rigid charged DNA fragment, where the
translocation free energy barrier can be easily computed; see Fig.
17
for a schematic
plot of the situation.
All simulations were performed both with and without use of the ICC* algorithm
[
199
] to investigate the influence of dielectric mismatch. In a recent article [
215
]
we employed coarse-grained Molecular Dynamics (MD) simulations to compute
the mean force acting on the DNA fragment, taking explicitly into account the
combined effect of the DNA counterions, salt ions at different ionic strengths, and
surface polarization charges generated by the presence of the dielectric mismatch.
It is straightforward then to calculate the free energy barrier by computing the
PMF acting on the center of mass of the model DNA along the pore axis. For this
reaction coordinate the Fixman potential [
216
] is constant, and the PMF can be
obtained by numerical integration of the mean force. The obtained PMFs are
shown in Fig.
18
. The free energy barrier in the salt-free case is strikingly higher
Fig. 17 The plot shows the schematic view of a charged rod confined to a finite nanopore. The
environment has a dielectric constant of 80, whereas the material of the nanopore itself has a
dielectric constant of 2. The inner part of the pore that is filled with water is also assumed to have a
dielectric constant of 80
Search WWH ::
Custom Search