MOLECULAR DYNAMICS STUDY OF
LIPOSOMES WITH
A NEW COARSE-GRAINEDMOLECULAR MODELWataru SHINODAAIST

2010/08/26

MULTI-SCALE MODELING
phenomenological modelingmolecularmodeling

CONTENTS
1. COARSE-GRAINED MOLECULAR MODELING
II. VESICLES
A. MORPHOLOGY OF LIPID ASSEMBLY
B. LIPID MIXING EFFECT
III. EFFECT OF CARBON NANOPARTICLES(FULLERENES) ON THE MEMBRANESSCALE ISSUE FOR
MOLECULAR SIMULATION
4"5#&!"#$%&'(#)*&+,-).
#&/)-"0!"#!$%&#!$"#!$'$%&#!$#!$#!$'(%#!$#!()+,-).#&/)-"0#%&!"#$%!&'#$()&*#(+',"0/&All atom

12-3#&

COARSE GRAINING PROCEDURE

MULTI-PROPERTY FITTING
Target properties:
Surface/interfacial tension, density, compressibility,
Solvation free energy, transfer free energy,
Radial distribution functions from all-atomic model

Simple potential functions
Intramolecular : harmonic
Versatility, transferability
Intermolecular : Coulomb + (LJ12-4 or LJ9-6)

Shinoda et al. Mol. Simul. (2007);
Soft Matter (2008); J. Phys. Chem. B (2010).

WHAT WE GAIN ... ?
•Mesophase structure•Self-assembly•Phase transition•Correct molecular partition(oil/water)•Transferability•Bulk solution•Interfaces (air/water, oil/water, solid/water etc.)•Systematic parameterization•Multiscale(AA-CG) / reverse mapping

CT!

ALKANE MODEL CM!
LJ9-6

CT2!

CT-CT

CH3CH2CH2-CH2CH2CH2CH3CH2-

CT2-CM
CT2-CT2

CT-CM
CM-CM

RDF: Dodecane

ALKANE-WATER INTERACTION
interfacepair

water/hexane

CT-W

water/nonane
water/dodecane

CM-W

water/pentadecanewater/heptane

CT2-W

interfacial tension
expMD

49.96

50.0

51.21

51.9

52.14

52.9

-52.9

50.30

50.1

ALKANE-WATER INTERACTION
TRANSFER FREE ENERGY

density profile across thehexane/water interface

SOLUTE-W INTERFACTION
Hydration free energyεEx) Ethylene glycol - water

Steered MD / Jarzynski or
Thermodynamic Integration

C12E2 LAMELLAR PHASE!"#$%!"#$%&'(')$**+,'-./0'1233456'
7489:'/2;<;,';3=6>'?','2'$9@' 01$%!%&%'()'%*+,%-%"%&%.(/)%*+%!%&%'()'%*+,%-%"%&%.(23%*+%

!!"

#$"

PHASE DIAGRAM C12E6!"!"!"

Jonsson et al., ‘Surfactants and Polymers in Aqueous Solution’PHOSPHATIDYLCHOLINE(PC):
LIPID BILAYER
CG-MD has carried out for 100ns
in the NPT ensemble
Area per lipid: A, repeat spacing: d, area expansion modulus: KA, bending modulus: ϰT [K]A [Å2]d [Å]KA [dyn/cm]

ϰ [10-20 J]

MD

Expt.

MD

Expt.

MD

Expt.

MD

Expt.

DMPC

310

62.0

60.6

60.0

⎯

226

234

6.90

5.6, ~10DPPC

323

63.8

64

66.9

67

233

⎯

6.41

~10POPC

303

64.6

6466.2⎯296⎯5.68⎯PHOSPHATIDYLETHANOLAMINE(PE)POPE BILAYER
T [K]
POPE308

A [Å2]d [Å]KA [dyn/cm]

ϰ [10-20 J]

MD

Expt.

MD

Expt.

MDExpt.

MD

Expt.

60.3

60

67.7

⎯296

⎯

6.45

⎯

34"505$#$67&%(')$67&"8&+,&)(9:('6)&
0#"'9&&61(&5$#07(4&'"4:0#

;0%$0#&%$)64$5<6$"'&8<'=6$"'&
0:"'9&1(0%94"<>&)(9:('6)

!"#$%&#$'()*&+,-./&/0)1(%&#$'()*&22-./

ORDER PARAMETER PROFILES!!"#$%&'()$*&+'',+#"-(.&/!&0"'(%&'()$*&."+12$,31+()$%&/!

MAKING A VESICLE

long time.......

MORPHOLOGY OF LIPID AGGREGATE(VESICLE, BICELLE)DMPC 1512

DMPC 1000VESICLE FORMATION (LARGER SYSTEMS)DMPC 3500

DMPC 5000

MORPHOLOGY CHANGE (DMPC)DMPC1000

Bicelle (disk)

DMPC1512

DMPC2500

Closed vesicle
DMPC3500

DMPC5000

Energy cost at the bilayer edge vs Bending free energy

BISTABILITY OF AGGREGATEDMPC 1512

Closed Vesicle

BicelleMicrosec. MD

ACKNOWLEDGMENTS✴CG modelingProf. Michael L Klein (Temple Univ.)
Prof. Russell DeVane (Temple Univ.)✴Implementation of CG model to LAMMPS
Prof. Axel Kohlmeyer (Temple Univ.)✴Free energy analysis
Prof. Steven Nielsen (Univ. Texas at Dallas)
Dr. Takenobu Nakamura (AIST)
T2K, Tsukuba Univ.
Next Generation Supercomputer Project
CREST-JST