1 |
mmeineke |
333 |
\documentclass[11pt]{article} |
2 |
|
|
|
3 |
|
|
\usepackage{graphicx} |
4 |
|
|
\usepackage{color} |
5 |
|
|
\usepackage{floatflt} |
6 |
|
|
\usepackage{amsmath} |
7 |
|
|
\usepackage{amssymb} |
8 |
|
|
\usepackage{subfigure} |
9 |
|
|
\usepackage{palatino} |
10 |
|
|
\usepackage[ref]{overcite} |
11 |
|
|
|
12 |
|
|
|
13 |
|
|
|
14 |
|
|
\pagestyle{plain} |
15 |
|
|
\pagenumbering{arabic} |
16 |
|
|
\oddsidemargin 0.0cm \evensidemargin 0.0cm |
17 |
|
|
\topmargin -21pt \headsep 10pt |
18 |
|
|
\textheight 9.0in \textwidth 6.5in |
19 |
|
|
\brokenpenalty=10000 |
20 |
|
|
\renewcommand{\baselinestretch}{1.2} |
21 |
|
|
\renewcommand\citemid{\ } % no comma in optional reference note |
22 |
|
|
|
23 |
|
|
|
24 |
|
|
\begin{document} |
25 |
|
|
|
26 |
|
|
|
27 |
|
|
\title{A Mesoscale Model for Phospholipid Simulations} |
28 |
|
|
|
29 |
|
|
\author{Matthew A. Meineke\\ |
30 |
|
|
Department of Chemistry and Biochemistry\\ |
31 |
|
|
University of Notre Dame\\ |
32 |
|
|
Notre Dame, Indiana 46556} |
33 |
|
|
|
34 |
|
|
\date{\today} |
35 |
|
|
\maketitle |
36 |
|
|
|
37 |
|
|
\section{Research Summary} |
38 |
|
|
|
39 |
|
|
Simulations of phospholipid bilayers are, by necessity, quite |
40 |
|
|
complex. The lipid molecules are large, and contain many atoms. Also, |
41 |
|
|
the head group of the lipid will typically contain charge separated |
42 |
|
|
ions which set up a large dipole within the molecule. Adding to the |
43 |
|
|
complexity are the number of water molecules needed to properly |
44 |
|
|
solvate the lipid bilayer, typically 25 water molecules for every |
45 |
|
|
lipid molecule. These factors make it dificult to study certain |
46 |
|
|
biologically interesting phenomena that don't fit within a short time |
47 |
|
|
or length scale. One such phenomenon is the existence of the ripple |
48 |
|
|
phase ($P_{\beta'}$) of the bilayer between the gel phase |
49 |
|
|
($L_{\beta'}$) and the fluid phase ($L_{\alpha}$). The $P_{\beta'}$ |
50 |
|
|
phase has been shown to have a ripple period of |
51 |
|
|
100-200~$\mbox{\AA}$.\cite{katsaras00,sengupta00} A simulation of this |
52 |
|
|
length scale would require approximately 1,300 lipid molecules in |
53 |
|
|
addition to all the water needed to fully solvate the bilayer. Another |
54 |
|
|
system of interest would be drug molecule diffusion through the |
55 |
|
|
membrane. Due to the fluid-like properties of a lipid membrane, not |
56 |
|
|
all diffusion takes place at membrane channels. It is of interest to |
57 |
|
|
study certain molecules that may incorporate themselves directly into |
58 |
|
|
the membrane. These molecules may then have an appreciable waiting |
59 |
|
|
time (on the order of nanoseconds) within the bilayer. |
60 |
|
|
|
61 |
|
|
\label{sec:ssdModel} |
62 |
|
|
|
63 |
|
|
\begin{figure} |
64 |
|
|
\centering |
65 |
|
|
\includegraphics[width=50mm]{ssd.epsi} |
66 |
|
|
\caption{The SSD model with the oxygen and hydrogen atoms drawn in for reference.} |
67 |
|
|
\label{fig:ssdModel} |
68 |
|
|
\end{figure} |
69 |
|
|
|
70 |
|
|
|
71 |
|
|
\label{sec:lipidModel} |
72 |
|
|
|
73 |
|
|
\begin{figure} |
74 |
|
|
\centering |
75 |
|
|
\includegraphics[angle=-90,width=80mm]{lipidModel.epsi} |
76 |
|
|
\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.} |
77 |
|
|
\label{fig:lipidModel} |
78 |
|
|
\end{figure} |
79 |
|
|
|
80 |
|
|
The mesoscale model used in this research is designed to simplify the |
81 |
|
|
number of calculations needed to properly simulate a phospholipid |
82 |
|
|
bilayer. The water molecules in the simulation are replaced with the |
83 |
|
|
Soft Sticky Dipole (SSD) model developed by Ichiye |
84 |
|
|
et. al.\cite{liu96:new_model,liu96:monte_carlo,chandra99:ssd_md} This |
85 |
|
|
model reduces water to a single point interaction, while still |
86 |
|
|
maintaining the hydrogen-bonding behavior of water. The lipid molecule |
87 |
|
|
itself is then modeled as a chain of ``tail'' atoms attached to a |
88 |
|
|
large ``head'' atom. The head atom contains a freely rotating dipole |
89 |
|
|
to eliminate the charge separation present in an actual phospholipid. |
90 |
|
|
|
91 |
|
|
In the attached images, one can see that the model demonstrates very |
92 |
|
|
promising initial results. In the images, the head atoms are colored |
93 |
|
|
blue, the tail atoms are colored gray, and the water molecules reduced |
94 |
|
|
in size for clarity. The actual simulation is enclosed within the |
95 |
|
|
bounding box. In the simulation containing only 25 lipid models, the |
96 |
|
|
system has demonstrated a spontaneous division into two leaflets, in |
97 |
|
|
route toward a bilayer. In the 50 model system, the lipids show |
98 |
|
|
spontaneous aggregation into micelles from a random initial |
99 |
|
|
configuration. Future aspects of the research will focus on the |
100 |
|
|
effects of tethering the orientation of the dipole, as well as |
101 |
|
|
increasing the scale of the systems studied to gain insight into bulk |
102 |
|
|
bilayer properties. |
103 |
|
|
|
104 |
|
|
\bibliographystyle{achemso} |
105 |
|
|
\bibliography{application} |
106 |
|
|
\end{document} |