Biomedical Engineering Reference
In-Depth Information
if continuum electrostatics theory provides the field inside the channel with sufficient
accuracy to get realistic currents, calculating the field is computationally challeng-
ing. Only recently was the important reaction field contribution (due to image forces
caused by moving permeating ions from a high to a lower dielectric environment)
incorporated in simulations of realistic 3D ion channel models [23, 32, 61].
2.2.4
Other methods
One of the biggest problems of PNP and its equilibrium sibling PB is probably that
the short-range potential of mean force is not correct, which leads to incorrect in-
teractions between ions and protein and between ions and other ions. Similarly, in
BD the short-range interactions between ions and ion and protein are not correct
because of the continuum representation of the solvent. However, there are other
theories, taken from the physical chemistry of ionic solutions, that go beyond PB
that improve on this aspect of the simulations. In principle, one would like to use a
theory that included e.g. the finite size of ions and single filing of ions and water,
using techniques from statistical mechanics of electrolytes. A number of interesting
recent papers have started to explore application of more advanced statistical me-
chanical approaches to channels and channel-like systems. These methods include
Monte Carlo [50], density functional theory [49], and calculations using the mean
spherical approximation for electrolytes [83]. Some applications of these methods
are reviewed below.
2.3
Selected applications
2.3.1
Simplified systems
Clearly, the availability of high-resolution ion channel structures has been the key
factor spurring rapidly growing interest in simulations and theory of ion channels.
Perhaps one of the most significant other developments in the rapidly growing in-
terest in the theory of ion channels is the influx of methods from other areas, such
as the physics and physical chemistry of fluids in confined geometries and of elec-
trolyte solutions. Initial efforts to combine these theories with biological problems
in the area of channels have already given very interesting results, and I think we can
expect much progress from continued work in this area. Simulations of simplified
pore models, ranging for inifinitely extended cylinders to artificial pores with atomic
detail, such as a carbon nanotubes, have contributed greatly to a better understanding
of basic physical principles that affect selectivity, diffusion, collective behavior of
ions and water in narrow pores and similar phenomena. Without trying to be exhaus-
tive, it is interesting to consider a few recent studies on highly idealized systems that
consider different aspects of simulations of channels.
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