Coarse-grain modeling of lipid membranes

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Presentation transcript:

Coarse-grain modeling of lipid membranes Mario Orsi University of Southampton LAMMPS workshop, Albuquerque, 9 August 2011 1

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

Membrane modeling Atomistic models: Coarse-Grain (CG) models: Water Lipid bilayer Water Atomistic models: Accurate but computationally demanding Coarse-Grain (CG) models: Orders of magnitude faster to simulate 3

CG models of lipids and water Klein et al CG models of lipids and water Klein et al., J Phys Chem B (2001); Smit et al., J Phys Chem B (2003); Marrink et al., J Phys Chem B (2004, 2007); Izvekov and Voth, J Phys Chem B (2005); Atomistic CG Headgroup: dipole moment ~ 20 D Ester/glycerol: dipole moments ~ 2 D CG Issues: Incomplete electrostatics Water: generic apolar fluid Lennard-Jones combination rules not followed: εAB ≠(εAεB)1/2 Look for atomistic model with partial charges highlighted 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 7

“Dual-resolution” systems Drugs & hormones [Soft Matter, 6, 3797 (2010)] Antimicrobial compounds [J R Soc Interface, 8, 826 (2011)]

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 field ELectrostatics-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 Potential Energy 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]: cut sf Force Derivative (force) Derivative (force) zoomed x10 Force zoomed x10

LAMMPS NVE simulation of point dipoles Shifted-force: better energy conservation + larger timesteps

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

ELBA in LAMMPS: membrane self-assembly 10 ns Water channel forms

ELBA in LAMMPS: membrane self-assembly 30 ns Water channel persists

ELBA in LAMMPS: membrane self-assembly 40 ns Water channel thinning

ELBA in LAMMPS: membrane self-assembly 50 ns Water channel disappears Remaining defect: “thread” of lipid headgroups

ELBA in LAMMPS: membrane self-assembly 60 ns Defect-free, stable bilayer

ELBA+LAMMPS perspectives More lipid species Cholesterol Lipid mixtures Microdomain (“raft”) formation Dual-resolution Atomistic proteins in CG membrane environment [From “The inner life of the cell”] 20

Acknowledgements Jonathan Essex Julien Michel Funding: UK taxpayers (University of Edinburgh) Wendy Sanderson Massimo Noro Funding: UK taxpayers J&J Unilever 21