Chemistry Reference
In-Depth Information
Figure 1
Bacterial chloride channel homolog (PDB code 1KPL). This transporter exists
as a homodimer—the plane separating the two dimers is oriented vertically in the middle
of this figure. The extracellular side is on top. The viewing direction is from the side, and
the two shaded areas are the rough locations of the boundaries of the membrane. The
two darkly shaded groups in each of the monomers are weak acid groups (glutamates,
E148 on top and E203 on the bottom), which are important for proton transport
through the structure. The E148 group also acts as a gate for chloride ion transport.
''magically'' perform this ion exchange? Both experiments
31,36
andmodeling stu-
dies
17
have begun to address this issue.
Several aspects of this membrane protein system require the use of multi-
scale modeling. Anion transport through the pore definitely requires a molecu-
lar-level treatment because the pore in the selectivity filter is close in size to
that of a single chloride ion, and protein fluctuations clearly play a role during
ion motion.
20
Electrostatic forces are crucial in anion selection, and the corre-
sponding interaction energies are very large. If a single ion is placed at a cen-
tral binding site in the pore, the free energy relative to that in water is tens of
kT
energy units lower; a second anion is required to enter the pore to desta-
bilize the first anion through repulsive interactions. Experiments indicate such
multiion transport.
37
One motivation for implementing a multiscale approach,
therefore, is that while the local interactions in the pore must be handled at the
molecular level, parts of the protein and the membrane far from the pore may
be treated in a time-saving, coarse-grained fashion. A second motivation is
simply that we need efficient solutions of the Poisson equation in determining
the electrostatic interactions for a given configuration. A third motivating
point concerns the gating mechanism: A glutamate (weak acid) residue is stra-
tegically situated at the extracellular entrance to the filter, and this gate
