Computer simulation of lipids and DNA using a coarse grain methodology

Abstract

The nucleus of the eukaryotic cell contains a large pool of lipids together with structural
proteins and genomic DNA. The project aim was to develop simple and robust lipid and
DNA models that will allow for these complex molecules to be mixed together in order to
elucidate the possible interactions. The large percentage of lipids found within the nucleus
makes it likely that they exist in aggregates, although the actual role and structure in which
they exist is unknown.

While there has not been substantial work done to model such interactions between lipids
and DNA in order to better understand the interactions within the nucleus, a substantial
body of work exists on lipid/DNA complexes in relation to gene therapy. These simulations
in many cases however, are too simple and the structures formed are pre-imposed to a certain
degree. Our model would attempt to simulate these interactions without such pre-imposed
conditions relying solely on interactions between the particles to drive the structures being
formed. A coarse graining approach in which several groups of atoms are subsumed into
single interaction sites was deemed suitable given the complexity of modelling a mixture of
DNA and lipids, together with the solvent and ion environment. In this regard new models
of lipids, DNA, ion and solvent models were developed in a purpose built molecular dynamics
package called LANKA-Lipid And Nucleic acid Komputer Algorithm.

The lipids in the model are represented as polar ellipsoids and the solvent as spheres with
dipoles embedded within them. The interactions between the lipids and solvent are modelled
using the Gay Berne potential. The developed lipid model was able to self assemble into a
stable bilayer phase and reproduce many bilayer properties of a liquid crystal phase. The
model was then extended to capture some of the other lipid phases seen in nature, including
lyotropic phase transitions.

A simple study of lipid mixtures has also been undertaken during this period. The
importance of considering multicomponent lipid systems has increasingly been highlighted in
the literature to make the lipid models more realistic. The developed lipid models are simple
enough to extend and attempt to simulate the formation of lipid rafts and domain formation.
Simulation of DNA in the past has largely focused on atomistic studies. While these have
proved valuable they do not consider the macroscopic length scales of the molecule. Simplified
models trying to capture long length scales have had to compromise on the molecular level
detail. Coarse grain models while trying to bridge the gap have also remained largely idealistic
in nature.

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Identifiers

ORCID for Jonathan W. Essex: orcid.org/0000-0003-2639-2746

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