Coarse-grained molecular dynamics versus mesoscale (dynamic) density functional theory for copolymer-vesicle self-assembly. Case study: sterically stabilized liposomes.

We carried out a series of Coarse-Grained Molecular Dynamics (CG-MD) simulations of liposome-copolymer systems in an attempt to understand the effect of copolymer structure and concentration on vesicle closure. Coarse graining implies fewer degrees of freedom, cheaper potential calculation, smoother potential surfaces and larger time steps. In this way reliability and accuracy of fine grained (FG) i.e. atomistic models is combined with the efficiency of a reduced representation. Such a powerful approach helped our million-atoms simulations to yield hundreds of nanoseconds trajectories starting from a randomized distribution of lipid molecules (1, 2-Dipalmitoyl-sn-glycero-3-phosphocholine – DPPC and Cholesterol molecules) plus varying concentration of polymers with lipid mimetic units in explicit solvent (order of million water molecules). Simulation data is successfully verified against experimental DOSY-NMR results.
However we are eager for further information beyond simply resolving the fact of copolymer-liposome emergence. Our sterically stabilized liposomes fall within mesoscopic ordering of scales and thus the problem belongs to spatial and temporal scales extending far beyond current computational capability for atomistic and even coarse-grained dynamics.
Thus the second part of our contribution reveals our preparation and strivings toward a mesoscale solution for our self-assembly questions. The aim of mesoscopic modelling is to address ordering intricate mechanisms without sacrificing molecular details to the phenomenological formalisms. Therefore one has to leave phenomenological expansion of the free energy in order parameters and instead define intrinsic free energy functionals based on a density distribution forcing external potentials to enter as Lagrange multiplier fields.