Coarse-grain modeling of lipid membranes Mario Orsi University of Southampton LAMMPS workshop,...

Coarse-grain modeling of Coarse-grain modeling of lipid membraneslipid membranes

Mario OrsiMario Orsi

University of SouthamptonUniversity of Southampton

LAMMPS workshop, Albuquerque, 9 August 2011LAMMPS workshop, Albuquerque, 9 August 2011

http://en.wikibooks.org/wiki/Structural_Biochemistry/Lipids/Lipid_Bilayer

Membrane modelingMembrane modeling

• Atomistic models:Atomistic models:– Accurate but computationally demandingAccurate but computationally demanding

• Coarse-Grain (CG) models:Coarse-Grain (CG) models:– Orders of magnitude faster to simulateOrders of magnitude faster to simulate

Water

Water

Lipidbilayer

CG models of lipids and waterCG models of lipids and waterKlein et al., Klein et al., J Phys Chem BJ Phys Chem B (2001); Smit et al., (2001); Smit et al., J Phys Chem BJ Phys Chem B (2003); (2003);

Marrink et al., Marrink et al., J Phys Chem BJ Phys Chem B (2004, 2007); (2004, 2007); Izvekov and Voth, J Phys Chem B (2005);

• CG Issues:CG Issues:– Incomplete Incomplete

electrostaticselectrostatics– Water: generic Water: generic

apolar fluidapolar fluid– Lennard-Jones Lennard-Jones

combination rules combination rules not followed: not followed: εεABAB ≠≠((εεAAεεBB))1/21/2

Atomistic CGHeadgroup:

dipole moment ~ 20 D

Ester/glycerol:dipole moments ~ 2 D

H2O:dipole moment ~ 3 D

Our CG model [Orsi et al, J Phys Chem B, 2008]

• Explicit electrostatics, relative dielectric constant r=1– Lipid: charges for headgroup and dipoles for glycerol/ester– Water: 1-site “SSD” dipolar model [Liu & Ichiye, J Phys Chem, 1996]

• Tails: anisotropic “liquid-crystal” potential [Gay and Berne, J Chem Phys, 1981]• Bespoke MD code developed in-house

Membrane properties

J Phys: Condens Matter, 22, 155106 (2010)

CG/atomistic multiscale simulation

• Fine chemical detail for

selected molecules• “Dual-resolution”

system of mixed granularities

• Our CG model compatible with atomistic potentials [Michel et al, J Phys Chem B, 2008; Orsi et al, J Phys Chem B, 2009]• Electrostatics: classical

Coulomb formulae

Drugs & hormones [Soft Matter, 6, 3797 (2010)]

Antimicrobial compounds[J R Soc Interface, 8, 826 (2011)]

“Dual-resolution” systems

Limitations of our methodology

Force field• Gay-Berne potential

(ellipsoidal tails)– Unrealistic

interdigitation when simulating solid (“gel”) bilayer phases

Software• Our bespoke code

– Not parallel– Not very flexible

• Using LAMMPS instead? Not straightforward:– No SSD water– Straight cutoff for

dipoles is problematic

New “ELBA” force fieldELectrostatics-BAsed coarse-graining

• Simplified water: LJ + dipole

• Lipid tails: LJ• Validated with in-

house program• For challenging

applications, the power of LAMMPS is needed!

• LAMMPS “dipole/cut” pair style– Straight cutoff: discontinuities

in potential and force– Poor energy conservation– Artefacts in the particles’

motion

• New shifted-force style (“dipole/sf”)– Modified formulae: potential &

force go to zero at the cutoff [Allen & Tildesley, 1987]:

Energy

Force

Force zoomed x10

Potential

Derivative (force)

Derivative (force)zoomed x10

cutsf

LAMMPS NVE simulation of point dipoles

Shifted-force: better energy conservation + larger timesteps

E

ELBA in LAMMPS: preliminary MD results

Membrane self-assembly

• Lipid/water dispersion

• Lipid heads: red• Lipid tails:

transparent yellow

• Water: blue

ELBA in LAMMPS: membrane self-assembly

• 2 ns• Phase

separation


• 10 ns• Water channel

forms



persists



thinning



disappears• Remaining

defect: “thread” of lipid headgroups


• 60 ns• Defect-free,

stable bilayer

ELBA+LAMMPS perspectivesELBA+LAMMPS perspectives

• More lipid More lipid speciesspecies– CholesterolCholesterol

• Lipid mixturesLipid mixtures– Microdomain Microdomain

(“raft”) (“raft”) formationformation

• Dual-resolutionDual-resolution– Atomistic Atomistic

proteins in CG proteins in CG membrane membrane environmentenvironment[From “The inner life of the cell”]

AcknowledgementsAcknowledgements

• Jonathan Essex Jonathan Essex • Julien Michel Julien Michel (University of Edinburgh)(University of Edinburgh)

• Wendy SandersonWendy Sanderson• Massimo NoroMassimo Noro

• Funding:Funding:– UK taxpayersUK taxpayers– J&JJ&J– UnileverUnilever

Coarse-grain modeling of lipid membranes Mario Orsi University of Southampton LAMMPS workshop,...

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