Computer simulations of biomolecules and membranes

The important properties of biological membranes such as elasticity and structure, and their interaction with nanoparticles is of great importance to nanomedicine applications such as drug delivery and gene therapy. This thesis reports on studies carried out using molecular dynamics (MD) simulations to investigate the physics and chemistry of POPC lipid bilayer membranes and their interactions with ions and nanoparticles. In this study two techniques were employed; all atomic (AA) and coarse grained (CG) MD simulations. In the first part of our investigations, the elastic properties of a 1-palmitoyl-2-oleoyl-snglycero- 3-phosphocholine (POPC) membrane with missing leaflets as well as a defect-free membrane were determined. The calculated bulk moduli compare well with the results of other researchers. Most interestingly, we established that the removal of a whole leaflet or half a leaflet does significantly affect the elastic properties. In studying of diffusivity of Na and Cl ions as well as of water molecules across a POPC membrane, we constructed systems to model the flow of ions across a membrane separating two different aqueous solutions. We were able to show that in order to force diffusion across the membrane, it was necessary to introduce an imbalance of positively and negatively charged ions on either side of the membrane. We have been able to confirm that the diffusion process takes place by the creation of a pore in the membrane. The diffusion coefficients of the ions have been determined from the mean square displacements (MSD) of the particles as a function of time. We found that both the Na and Cl ions diffuse rapidly through the pore with diffusion coefficients ten times larger than in water. Also, we observed that although the Na ions are the first to begin the permeation process due to the lower potential barrier it experiences, the Cl ions complete the permeation across the barrier more quickly due to their faster diffusion rates. AAMD simulations were carried out to determine the adsorption sites of neutral and charged gold nanoparticles on the surface of the POPC membrane in order to understand the first step of translocation process. We have found that the adsorption of a neutral gold nanoparticle is more likely than that of a charged nanoparticle. We were also able to demonstrate the partial penetration of a neutral nanoparticle through the surface of the POPC membrane. CGMD was used to study the stability of a carbon nanotube (CNT) inside the POPC lipid bilayer membrane. We found that the CNT was indeed stable inside the POPC membrane suggesting that such nanotubes could be used as a targeted drug delivery