Molecular dynamics simulation of membrane channels
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Molecular Dynamics Simulation of Membrane Channels. Part III. Nanotubes Theory, Methodology. Summer School on Theoretical and Computational Biophysics June 2003, University of Illinois at Urbana-Champaign http://www.ks.uiuc.edu/training/SumSchool03/.

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Molecular Dynamics Simulation of Membrane Channels

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Molecular dynamics simulation of membrane channels

Molecular Dynamics Simulation of Membrane Channels

Part III. Nanotubes

Theory, Methodology

Summer School on Theoretical and Computational Biophysics

June 2003, University of Illinois at Urbana-Champaign

http://www.ks.uiuc.edu/training/SumSchool03/


Carbon nanotubes hydrophobic channels perfect models for membrane water channels

Carbon NanotubesHydrophobic channels - Perfect Models for Membrane Water Channels

A balance between the size and hydrophobicity


Carbon nanotubes hydrophobic channels perfect models for membrane water channels1

Carbon NanotubesHydrophobic channels - Perfect Models for Membrane Water Channels

  • Much better statistics

  • No need for membrane and lipid molecules


Carbon nanotubes hydrophobic channels perfect models for membrane water channels2

Carbon NanotubesHydrophobic channels - Perfect Models for Membrane Water Channels

  • Much better statistics

  • No need for membrane and lipid molecules


Water single files in carbon nanotubes

Water Single-files in Carbon Nanotubes

Water files form polarized chains in nanotubes


Water nanotube interaction can be easily modified

Water-Nanotube Interaction can be Easily Modified

Hummer, et. al., Nature, 414: 188-190, 2001


Calculation of diffusion permeability from md

Calculation of Diffusion Permeability from MD

0: number of water molecules crossing the channel from the left to the right in unit time

0 can be directly obtained through equilibrium MD simulation by counting “full permeation events”


Liposome swelling assay

Liposome Swelling Assay

carbohydrate

440 nm

H2O

carbohydrate +

H2O

shrinking

reswelling

scattered light

lipid vesicles

100 mM Ribitol

GlpF is an aquaglyecroporin: both water and carbohydrate can be transported by GlpF.

channel-containing proteoliposomes


Chemical potential of water

Chemical Potential of Water

pure

water

pure

water

W

W

(1)

(2)

membrane

Water flow in either direction is the same, i.e., no net flow of water.


Solutes decrease the chemical potential of water

Solutes Decrease the Chemical Potential of Water

Addition of an impermeable solute to one compartment drives the system out of equilibrium.

dilute

solution

pure

water

W+S

W

(1)

(2)

Water establishes a net flow from compartment (2) to compartment (1).

Semipermeable

membrane


Establishment of osmotic equilibrium

Establishment of Osmotic Equilibrium

At equilibrium, the chemical potential of any species is the same at every point in the system to which it has access.

dilute

solution

pure

water

W+S

W

(1)

(2)

Semipermeable

membrane


Establishment of an osmotic equilibrium

Establishment of an Osmotic Equilibrium

Solute molar fraction in physiological (dilute) solutions is much smaller than water molar fraction.

dilute

solution

pure

water

W+S

W

(1)

(2)

Semipermeable

membrane

Osmotic pressure


Establishment of an osmotic equilibrium1

Establishment of an Osmotic Equilibrium

dilute

solution

pure

water

Solute concentration (~0.1M) in physiological (dilute) solutions is much smaller than water concentration (55M).

W+S

W

(1)

(2)


Osmotic flow of water

Osmotic Flow of Water

dilute

solution

pure

water

Net flow is zero

W+S

W

(1)

(2)

Volume flux of water

Hydraulic permeability

Osmotic permeability

Molar flux of water


Molecular dynamics simulation of membrane channels

Simulation of osmotic pressure induced water transport may be done by adding salt to one side of the membrane.

NaClNa++Cl-

(1)

Semipermeable

membrane

(2)

There is a small problem with this setup!


Molecular dynamics simulation of membrane channels

Problem: The solvents on the two sides of a membrane in a conventional periodic system are connected.

(1)

(1)

(1)

(2)

(2)

(2)

(1)

(1)

(1)

(2)

(2)

(2)

(1)

(1)

(1)

(2)

(2)

(2)


Molecular dynamics simulation of membrane channels

NaCl

We can include more layers of membrane and water to create two compartment of water that are not in contact

(1)

Semipermeable

membrane

(2)

Semipermeable

membrane

(1)


Molecular dynamics simulation of membrane channels

U N I T C E L L

NaCl

(1)

Semipermeable

membrane

(2)

Semipermeable

membrane

NaCl

(1)


Molecular dynamics simulation of membrane channels

Realizing a Pressure Difference in a Periodic System

membrane

water

membrane

water

membrane

Fangqiang Zhu

f is the force on each water molecule,

for n water molecules

The overall translation of the system is prevented by applying constraints or counter forces to the membrane.

F. Zhu, et al., Biophys. J. 83, 154(2002).


Molecular dynamics simulation of membrane channels

Applying a Pressure Difference Across the Membrane

Applying force on all water molecules.

Not a good idea!


Molecular dynamics simulation of membrane channels

Applying a Pressure Difference Across the Membrane

Applying force on bulk water only.

Very good


Molecular dynamics simulation of membrane channels

Applying a Pressure Difference Across the Membrane

Applying force only on a slab of water in bulk.

Excellent

Pf can be calculated from these simulations


Molecular dynamics simulation of membrane channels

Calculation of osmotic permeability of water channels

Aquaporin-1

GlpF

pf: 7.0 ± 0.9  10-14 cm3/s

Exp: 5.4 – 11.7  10-14 cm3/s

pf: 1.410-13 cm3/s


Stereoselective transport of carbohydrates by glpf

Stereoselective Transport of Carbohydratesby GlpF

Some stereoisomers show over tenfold difference in conductivity.

stereoisomers


Channel constriction

Channel Constriction

GlpF + glycerol

GlpF + water

red < 2.3 Å

2.3 Å > green > 3.5 Å

blue > 3.5 Å

HOLE2: O. Smart et al., 1995


Molecular dynamics simulation of membrane channels

Selectivity filter


Interactive molecular dynamics

Interactive Molecular Dynamics

VMD

NAMD


Observed induced fit in filter

Observed Induced Fit in Filter


Confinement in filter

Confinement in Filter

  • Selection occurs in most constrained region.

  • Caused by the locking mechanism.

RMS motion in x and y

z (Å)

Filter

region


Molecular dynamics simulation of membrane channels

Evidence for Stereoselectivity

Ribitol

Optimal hydrogen bonding and hydrophobic matching

Arabitol

10 times slower


Dipole reversal in channel

Dipole Reversal in Channel

  • Dipole reversal pattern matches water.

  • Selects large molecules with flexible dipole.

z (Å)

cos(dipole angle with z)

Dipole

reversal

region


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