Transcript MD-application2-ion

Mei Shi
Advisor-Dr. Balbuena
University of South Carolina
REU-Summer of 2002
Introduction
Ion channels are important not only for biological functions such
as electrical signal conductance, but also for applications in fuel
cells and batteries.
The design of the ion channel is modeled after KcsA potassium
ion channel from the bacteria known as Streptomyces lividans.
Molecular Dynamic Simulations involves the calculation of
molecular motions with respect to time based on a set of initial
conditions.
Computational software called DL_POLY2 is used. Input files
like CONFIG, FIELD and CONTROL are necessary to run the
simulation.
.
Background Information
4 identical protein subunits
Each subunit is consisted of 3
helical segments : outer helix,
inner helix, and pore helix.
Schematic picture of the KcsA Potassium Ion channel
4 carbonyl oxygen atoms are exposed to the extracellular environment.
Displace half of the ion’s hydration shell
The carbonyl oxygen atoms in the filter acts a surrogate water oxygen
that form the hydration shell.
The selectivity filter is formed by a amino acid sequence known as the
K+ channel’s signature sequence
K+ channel must mediate the transfer of a K+ ion from
its hydrated state in solution to its dehydrated state in the
selectivity filter.
K+ channel must favorably select K+ ion over Na +
(factor of 10000 to 1).
Potassium ion
Sodium ion
Charge---+1
Charge---+1
Radius---1.33 Å
Radius---0.95 Å
Theory of selectivity
Ion in solution is surrounded by waters of hydration. The
smaller the ion, the more highly localized its charge and
stronger the electric field, which makes smaller Na+ exert a
stronger attraction on the water surrounding and obtain a
smaller size of hydration shell than the bigger K+ does.
The diameter of the selectivity filter is
just enough allowing the dehydrated
K+ ion through, but is too wide for the
Na+ ion to bind and enter the filter and
too narrow for the hydrated Na+ ion to
pass through.
The selectivity of the potassium ion channel for K+ over Na+ can
be investigated by adjusting the diameter of the selectivity filter
and the positions of the charged pseudoatoms lining the filter.
A General Representation of the Cellular Environment
Cellular membrane---layers of neutral pseudoatoms that have the
characteristics of methane molecule such as their weight (16.00
au) and their Van der Waal sradius (1.95 Å)
Ion channel---a cylindrical pore that is embedded in the
membrane layer. The selective region of the pore is lined with
charged pseudoatoms that exhibit characteristics of carbonyl
oxygen atom on a peptide backbone such as their charge (-0.38).
SPC model of water molecules are placed on both sides of the
membrane as well as inside the channel along with different types
of ions such as chlorine ion, sodium ion and potassium ion.
Square anti-prism
Top view
Side view
water
Cl-
Filter atoms
K+
Membrane
Na+
500 steps
apart or
0.5 ps
apart
500
steps
apart
Or 0.5
ps apart
A better side view
Result and discussion
The diameter of the filter arranged from 4.7 Å to 7.9 Å,
and so far the result have yet to show selectivity.
Ion passage through the channel seems to depend only on
their initial positions and their charge.
Single file motion for water as well as ions was exhibited
in passing through the channel.