(104c) Multiscale Modeling for Phospholipid Bilayer Simulations

Multiscale Modeling for Phospholipid
Bilayer Simulations

A multiscale modeling
approach was used to develop an implicit-solvent intermediate-resolution model
to simulate the behavior of the lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in
water.  By reducing the DPPC
representation to 14 coarse-grained sites with unique properties, treating
solvent implicitly, and employing discontinuous molecular dynamics, a very fast
alternative to traditional molecular dynamics, we are able to simulate the
spontaneous formation of a bilayer from a random solution of 512 DPPC molecules
in several hours on a fast workstation.  Data used to calculate the coarse-grained model parameters
was obtained by running united-atom simulations with GROMACS.  Radial distribution functions were
plotted for all pairs of non-bonded coarse-grained sites to estimate the
hardsphere and square-well diameters. 
The interaction energy between each pair of non-bonded coarse-grained
sites was calculated using the Boltzmann inversion scheme.  The relative stiffness of each lipid is
maintained by imposing pseudobonds, which limit the bond lengths to fluctuate
by the same amount observed in the united atom simulations.  In the model each coarse-grained site
has its own realistic mass.  Simulation
results show that the model accurately reproduces structural properties of the
DPPC bilayer including the area per lipid, bilayer thickness, bond order and
mass density profiles.  Current
work is focused on extending the model to lipid mixtures and simulating the
phase separation that occurs as a bilayer composed of DPPC and 1,2-dipalmitoyl-sn-glycero-3-phosphate (PA) changes from
an initially-homogeneous state (at neutral pH) to a phase-separated state at
low pH.