This proposal asks for support to investigate the behavior of assemblies of amphiphilic molecules using computer simulation techniques. Amphiphiles are molecules with polar head groups and hydrocarbon tails. They are constituents of soaps and detergents (fatty acids), and cellular and model biomembranes (phospholipids). Over the past decade, computer simulation has emerged as an important complement to real experiments in the study of such complex systems. It is proposed to use realistic intermolecular potential models and molecular dynamics calculations to study the structure and dynamics of assemblies of amphiphiles. Particular emphasis will be placed on the intramolecular structure of the alkyl chains (gauche/trans isomerisation) and the nature of intermolecular chain-chain positional and orientational correlations in these systems. While the long-term objective is to study phospholipids which have two alkyl chains, the initial work will focus on assemblies of fatty acids with one chain per head group. The specific systems to be studied by molecular dynamics include the following: a) monolayers of amphiphilic molecules (fatty acids) supported on an inert substrate, such as glass (Langmuir-Blodgett films). b) monolayers and bilayers of amphiphilic molecules supported on an alkylated glass substrate (model biomembrane). c) monolayers of amphiphilic molecules at the air/water interface (Langmuir films). Of particular interest is the characterization of the so-called gel phase that occurs before the solidification of the monolayer. d) quasi-spherical aggregates of amphiphilic molecules in aqueous solution (micelles) and lamellar aggregates, with emphasis on the nature of the head group solvation and chain conformations. The eventual goal is to obtain structural and dynamical information on the behavior of amphiphilic assemblies that complements experiments currently underway at the University of Pennsylvania, and elsewhere, on the structure and function of (model) biomembranes and related systems.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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University of Pennsylvania
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Donald, Jason E; Zhang, Yao; Fiorin, Giacomo et al. (2011) Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion. Proc Natl Acad Sci U S A 108:3958-63
Delemotte, Lucie; Treptow, Werner; Klein, Michael L et al. (2010) Effect of sensor domain mutations on the properties of voltage-gated ion channels: molecular dynamics studies of the potassium channel Kv1.2. Biophys J 99:L72-4
Shinoda, Wataru; DeVane, Russell; Klein, Michael L (2010) Zwitterionic lipid assemblies: molecular dynamics studies of monolayers, bilayers, and vesicles using a new coarse grain force field. J Phys Chem B 114:6836-49
Pantano, Diego A; Klein, Michael L (2009) Characterization of membrane-protein interactions for the leucine transporter from Aquifex aeolicus by molecular dynamics calculations. J Phys Chem B 113:13715-22
Hénin, Jérôme; Shinoda, Wataru; Klein, Michael L (2009) Models for phosphatidylglycerol lipids put to a structural test. J Phys Chem B 113:6958-63
Devane, Russell; Shinoda, Wataru; Moore, Preston B et al. (2009) A Transferable Coarse Grain Non-bonded Interaction Model For Amino Acids. J Chem Theory Comput 5:2115-2124
Treptow, Werner; Tarek, Mounir; Klein, Michael L (2009) Initial response of the potassium channel voltage sensor to a transmembrane potential. J Am Chem Soc 131:2107-9
Khurana, Ekta; DeVane, Russell H; Kohlmeyer, Axel et al. (2008) Probing peptide nanotube self-assembly at a liquid-liquid interface with coarse-grained molecular dynamics. Nano Lett 8:3626-30
Klein, Michael L; Shinoda, Wataru (2008) Large-scale molecular dynamics simulations of self-assembling systems. Science 321:798-800
Domene, Carmen; Klein, Michael L; Branduardi, Davide et al. (2008) Conformational changes and gating at the selectivity filter of potassium channels. J Am Chem Soc 130:9474-80

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