1P111
Molecular Self-Assembly Behavior in Simple Lipid as Membrane Modeland its Stability using Molecular Dynamics Simulation
Acep Purqon, Ayumu Sugiyama, Hidemi Nagao, Kiyoshi Nishikawa
Division of Mathematical and Physical Science
Graduate School of Natural Science and Technology, Kanazawa University【INTRODUCTION】
Self-assembly is a process that generates higher order complexes fromsimpler molecular building blocks. This mechanism plays a crucial role toform biological membrane due to the hydrophobic effect of lipid that consistof hydrophobic and hydrophilic features. Membranes were introduced as fluidmosaic model, but recently we know that membranes are more mosaic than
fluid [1]. It implies that membrane structure is more complicated than thought
before. Furthermore there are some limitations of experiment to describe theprocess of self-assembly. For this reason we investigate the properties ofself-assembly using molecular dynamics simulation. Due to some interesting
characteristics and availability of experiment data for comparison, we choose
POPC (1-palmitoyl-2-oleoyl- phosphatidycholine) and POPE (1-palmitoyl2-oleoyl- phosphatidylethanolamine) as lipid molecule shown in Fig. 1 and 2[2,3].
FIGURE 1. POPC lipid

POPC

POPE
FIGURE 2. Molecular structure of POPC and POPE.

【METHOD】
In this simulation, lipid and water molecules are calculated in 3D and microcanonicalensemble NPT using AMBER program package [4] with force field 03 and TIP3P water. The
initial structure of lipid model is generated by VMD software shown in Fig. 3. At first we
determine the force field parameters and charge distributions by antechamber. In this study, weadopt the AM1-bcc charge for charge determine method. Lipid model are simulated in variouscondition. In this case, we simulate a) POPC in water b) POPC in salted water c) POPE in water,d) POPE in salted water. Each simulation is carried out in 300 K and 340 K under periodic
boundary condition. Therefore we perform 8 simulations to investigate environment andtemperature effects.

FIGURE 3. Initial coordinate of POPC lipid【ANALYSIS】
We report the following issues: a) From the snapshot of MD simulation, we can classify theself-assembly structure into micelle, vesicle and membrane. We start with POPC lipid
minimization in water environment and calculate RMSD as shown in Fig 4. b) We investigate
the temperature effect in the formation of self-assembly c) We calculate: free energy, root meansquare deviation (RMSD), radius of gyration (Rg), time relaxation, occurrence of cluster phasetransition, lipid density and population lipid to distance. These parameters are calculated toobtain quantitatively the behavior of self-assembly. d) Finally we discuss the additional effect ofsalt environment on stability of structure [5,6]. This analysis is important to know what
conditions make the lipid stable to form membrane. We focus on the explanation ofself-assembly behavior, some properties related to this model and stability of structureformation.
This preliminary result can be used for our future work to simulate the stability ofself-assembly in more complicated membrane structure as starting point in order to understandimportant problem in the relation between membrane structure and immune systems.

FIGURE 4. RMSD in POPC lipidReferences[1] D.M. Engelman, Nature, 438, 7068, (2005)[2] K. Mori, et al. Chem-BioInformatics J, 4, 15 (2004).
[3] T. Rog, et al. Acta Biochimica Polonica. 50, 789 (2003).
[4] D.A.Pearlman, D.A.Case, J.W.Caldwell, W.S.Ross, T.E.Cheatham, Ⅲ, S. DeBolt, D. Ferguson, G.
Seibel & P. Kollman. AMBER, a package of computer programs for applying molecular mechanics,normal mode analysis, molecular dynamics and free energy calculations to simulate the structural andenergetic properties of molecules. Comp. Phys. Commun. 91, 141 (1995).
[5] P. Mukhopadhyay, L. Monticelli, D.P. Tieleman, Biophysical J. 86, 1601 (2004).
[6] L. Vigh, et al. Progress in Lipid Research. 44, 303 (2005).