This proposal asks for support to Investigate the behavior of assemblies of amphiphilic molecules, using computer simulation techniques. Amphiphiles are molecules with polar headgroups 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 isomerization) 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 studied by molecular dynamics include the following: a) monolayers and bilayers of amphiphilic molecules (fatty acids) supported on hydrophobic or hydrophilic substrates (model biomembranes). b) monolayers of amphiphilic molecules at the air/water interface (Langmuir films). Of particular interest, is the characterization of the effects of density and temperature on phases that occur before the complete solidification of the monolayer. c) quasi-spherical aggregates of amphiphilic molecules in aqueous solution (micelles) with emphasis on the nature of the head-group solvation, chain conformations, and solubilization phenomena. d) bilayer and lamellar aggregates of amphiphilic molecules in aqueous solution. 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 (Professors J. K. Blasie and S. J. Opella), and elsewhere, on the structure and function of (model) biomembranes and related systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040712-05
Application #
3298543
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1988-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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

Showing the most recent 10 out of 31 publications