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\begin{document} |
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\title{A Mesoscale Model for Phospholipid Simulations} |
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\author{Matthew A. Meineke\\ |
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Department of Chemistry and Biochemistry\\ |
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University of Notre Dame\\ |
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Notre Dame, Indiana 46556} |
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\date{\today} |
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\maketitle |
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\section{Research Summary} |
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Simulations of phospholipid bilayers are, by necessity, quite |
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complex. The lipid molecules are large, and contain many atoms. Also, |
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the head group of the lipid will typically contain charge separated |
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ions which set up a large dipole within the molecule. Adding to the |
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complexity are the number of water molecules needed to properly |
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solvate the lipid bilayer, typically 25 water molecules for every |
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lipid molecule. These factors make it dificult to study certain |
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biologically interesting phenomena that don't fit within a short time |
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or length scale. One such phenomenon is the existence of the ripple |
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phase ($P_{\beta'}$) of the bilayer between the gel phase |
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($L_{\beta'}$) and the fluid phase ($L_{\alpha}$). The $P_{\beta'}$ |
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phase has been shown to have a ripple period of |
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100-200~$\mbox{\AA}$.\cite{katsaras00,sengupta00} A simulation of this |
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length scale would require approximately 1,300 lipid molecules in |
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addition to all the water needed to fully solvate the bilayer. Another |
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system of interest would be drug molecule diffusion through the |
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membrane. Due to the fluid-like properties of a lipid membrane, not |
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all diffusion takes place at membrane channels. It is of interest to |
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study certain molecules that may incorporate themselves directly into |
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the membrane. These molecules may then have an appreciable waiting |
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time (on the order of nanoseconds) within the bilayer. |
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\label{sec:ssdModel} |
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\begin{figure} |
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\centering |
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\includegraphics[width=50mm]{ssd.epsi} |
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\caption{The SSD model with the oxygen and hydrogen atoms drawn in for reference.} |
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\label{fig:ssdModel} |
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\end{figure} |
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\label{sec:lipidModel} |
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\begin{figure} |
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\centering |
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\includegraphics[angle=-90,width=80mm]{lipidModel.epsi} |
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\caption{A representation of the lipid model. $\phi$ is the torsion angle, $\theta$ is the bend angle, $\mu$ is the dipole moment of the head group, and n is the chain length.} |
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\label{fig:lipidModel} |
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\end{figure} |
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The mesoscale model used in this research is designed to simplify the |
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number of calculations needed to properly simulate a phospholipid |
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bilayer. The water molecules in the simulation are replaced with the |
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Soft Sticky Dipole (SSD) model developed by Ichiye |
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et. al.\cite{liu96:new_model,liu96:monte_carlo,chandra99:ssd_md} This |
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model reduces water to a single point interaction, while still |
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maintaining the hydrogen-bonding behavior of water. The lipid molecule |
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itself is then modeled as a chain of ``tail'' atoms attached to a |
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large ``head'' atom. The head atom contains a freely rotating dipole |
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to eliminate the charge separation present in an actual phospholipid. |
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In the attached images, one can see that the model demonstrates very |
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promising initial results. In the images, the head atoms are colored |
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blue, the tail atoms are colored gray, and the water molecules reduced |
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in size for clarity. The actual simulation is enclosed within the |
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bounding box. In the simulation containing only 25 lipid models, the |
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system has demonstrated a spontaneous division into two leaflets, in |
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route toward a bilayer. In the 50 model system, the lipids show |
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spontaneous aggregation into micelles from a random initial |
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configuration. Future aspects of the research will focus on the |
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effects of tethering the orientation of the dipole, as well as |
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increasing the scale of the systems studied to gain insight into bulk |
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bilayer properties. |
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\bibliographystyle{achemso} |
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\bibliography{application} |
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\end{document} |
