Proteinmembrane association'

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Protein-membrane association.

• Theoretical model, Lekner summation

A.H. Juffer The University of Oulu Finland-Suomi
A.H.Juffer The University of Oulu Finland-Suomi
A.H.Juffer The University of Oulu Finland-Suomi
A.H.Juffer The University of Oulu Finland-Suomi
A.H.Juffer The University of Oulu Finland-Suomi
A.H.Juffer The University of Oulu Finland-Suomi
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Previous work

• W. Xin and A.H. Juffer, Polarization and
  dehydration effects in protein-membrane
  association, To Be Submitted, 2004
• W.Xin and A.H. Juffer, A BEM formulation of
  biomolecular interaction, To Be Submitted, 2004
• C.M. Shepherd, H.J. Vogel and A.H. Juffer, Monte
  Carlo and molecular dynamics studies of
  peptide-bilayer binding, in High Performance
  Computing Systems and Applications 2000 (Nikitas
  J. Dimpoulos and Kin F. Li, Eds.), Kluwer
  Academic Publishers (Dordrechts, The
  Netherlands), Chapter 29, 447-464, 2002.
• C.M. Shepherd, K.A. Schaus, H.J. Vogel and A.H.
  Juffer, A Molecular Dynamics Study of
  Peptide-Bilayer Adsorption. Biophys. J. 80,
  579-596, 2001.
• A.H. Juffer, C.M. Shepherd and H.J. Vogel,
  Protein-membrane electrostatic interactions
  Application of the Lekner summation technique. J.
  Chem. Phys. 114, 1892-1905, 2001.
• A.H. Juffer, J. de Vlieg and P. Argos, Adsorption
  of Proteins onto Charged Surfaces A Monte Carlo
  Approach with Explicit Ions. J. Comput. Chem.,
  17, 1783-1803, 1996.

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Background

• Interactions between lipid molecules and proteins
  crucial role in regulation biological function.
• Membrane proteins
• Integral proteins e.g. photosynthetic reaction
  center
• Fully embedded into membrane
• Peripheral proteins e.g. phospholipase C-?1
• Only weakly bound to surface, separable by change
  in pH or ionic strength

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Background

• Understanding the physics of protein-lipid
  interactions leads to deeper insight

Equilibrium constant ? Standard free energy
THERMODYNAMICS, NOT MECHANISM
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Modeling protein-membrane binding
lipid bilayers
sandostatin
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Free energy of binding
Conformational Change.
Non-polar hydrophobic effect (expulsion of
non-polar compounds from water
Changes in motional degrees of freedom.
Difference in dielectric properties between water
and hydrocarbon region (mutual polarization
effects).
Direct electrostatic interaction between basic
residues and anionic lipids.
Changes inside membrane.
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Coulomb interaction
rij


Long-ranged beyond dimension of protein
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How to calculate it?
Assume periodicity along x, y-direction
Lx
Ly
q
Image
Ly
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The Lekner Summation
Conditionally converging sum
Fast absolutely converging sum
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Four surface charges potential
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Four surface charges field
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• Ions next to flat surface
• carrying a negative surface
• charge density.
• Accumulation of Na.
• Depletion of Cl-.
• Electric moment pointing
• towards flat surface.
• Symmetry along x- and y-axis
• but not along z-axis.

z-axis
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Ion densities near POPC
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Ion densities near POPG
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Free energy of adsorption
Change in free energy in moving protein from bulk
solution at z-? to A point zz0 near the surface
Thermodynamic integration
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Electrostatic force acting on Sandostatin
POPC
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Force acting on Sandostatin, MD
POPC
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Movie
The first 2 ns of a 6 ns MD simulation.
Biophys. J. 80, 579-596, 2001.
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Electrostatic force acting on Sandostatin
POPG
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Two solutes A, B immersed in polarizable solvent S
Q
Solvent
cavity
q
B
A
approximation
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Two polarisable objects
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Future improvements

• Inclusion of internal (essential) degrees of
  freedom.
• Dynamical simulations
• Stochastic modeling of proteins
• Effects of pH.

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Acknowledgements

• Weidong Xin
• Craig Shepherd

• Heritage Foundation
• Human frontiers
• MRC
• Biocenter
• Academy of Finland.