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.