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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 - PowerPoint PPT Presentation
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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
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
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.
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
Background
Understanding the physics of protein-lipid interactions leads to deeper insight
GK
Equilibrium constant↕
Standard free energy
THERMODYNAMICS, NOT MECHANISM
Modeling protein-membrane binding
lipid bilayers sandostatin
Free energy of binding
lipimmconqEelcnp GGGGGGG
Non-polar hydrophobic effect (expulsion of
non-polar compounds from water
Direct electrostatic interactionbetween basic residues and
anionic lipids.
ConformationalChange.
Difference in dielectricproperties between water and hydrocarbon region
(mutual polarization effects).
Changes in motionaldegrees of freedom.
Changes inside membrane.
Coulomb interaction
rij
++
ji
ji
q
rrr
04
3
04ji
jiji
q
rr
rrrE
jiij
ij
jiijel
r
r
qqrU
rr
04
Long-ranged: beyond dimension of protein
How to calculate it?
Assume periodicity along x, y-direction
q
Image
Ly
Lx
yxLL
q
Ly
The Lekner Summation
v vrr
vrrF 3
04 ji
jijiij qq
Conditionally
converging sum
ddqL
L
y
L
z
L
L
zk
L
yfKn
L
x
L
qqU
ji
x
ji
yyx
ji
n
k
k xyxx
jiij
for 2
2ln4
2cos2coshln4
22cos
00
0
1
2
122
20
0
Fast absolutelyconverging sum
ijii UF
Four surface charges: potential
Four surface charges: field
• 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
Ion densities near POPC
Ion densities near POPG
Free energy of adsorption
00 )()('
'zz
z
zUdz
z
zAdzA
)(')()('
)('
1)('zF
z
zU
z
zQ
zQkT
z
zA
kT
zUddddCzQ
,,,,exp)sin()('
rr
Change in free energy in moving protein from bulk solution at z=- toA point z=z0 near the surface:
)('ln)(' zQkTzA
Thermodynamic integration
Electrostatic force acting on Sandostatin
POPC
Force acting on Sandostatin, MD
POPC
Movie
The first 2 ns of a 6 ns MD simulation.Biophys. J. 80, 579-596, 2001.
Electrostatic force acting on Sandostatin
POPG
Two solutes A, B immersed in polarizable solvent S
q
Q
Solvent
A
B
lk lk
Bl
Ak
S
jj
AjA
jBj
SB
ii
BiB
iAi
SAel
n
nSBAW
,0
21
0
21
0
4
1
11
11,,
rr
int
approximation
cavity
dW ED2
1
Two polarisable objects
Future improvements
Inclusion of internal (`essential’) degrees of freedom.
Dynamical simulations Stochastic modeling of proteins Effects of pH.
Acknowledgements
Weidong Xin Craig Shepherd
Heritage Foundation
Human frontiers MRC Biocenter Academy of
Finland.
