2008 alberta nanotech...
TRANSCRIPT
2008 Alberta Nanotech Showcase
November 20, 2008
Maria StepanovaResearch Officer
Principal InvestigatorNINT
Modeling of Nanostructures :Bionanosystems, Polymers, and Surfaces
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How ?...Mesoscale kinetic modeling,
Kinetic Monte-Carlo,Self-consistent field theory (SCFT),Generalized Langevin dynamics,
Multivariate analysis of molecular dynamics trajectories.Whenever possible, we parameterize our models through a multiscale approach
combining into an integrated hierarchical system various levels of modeling, starting from molecular and atomic properties.
So that we can understand, predict, and directstructural organization
in natural and engineered nanosystems
What for ?...
We develop numeric tools for nanotechnology
Examples :
See our posters !
Synthesis Nanopatterns Mesophases Nanodomains Dynamic structure of Nanocrystals in Polymers of amphiphilic in lipid membranes of Proteins
surfactants
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Mesophases of Amphiphilic Surfactants
http://srs.dl.ac.uk
DPPC
http://static.howstuffworks.com
Dispersion aids and emulsifiers;Components in detergents, shampoos, soaps,and more...
Branched phospholipids are the major componentof bio-membranes
A surfactant molecule contains a hydrophilic head group and hydrophobic tail.
In water surfactants form micelles, lamellae, and mesophases.
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A self-consistent iterative procedure (SCFT)generates equilibrium distributions
of the components
Equilibrium Morphologies of Branched Lipids at Air-Water Interfaces
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Lipid tail
Lipid head
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Branched Initial distribution:lipid random mix of lipids, water, and air
Lipid membranes self-organizeat air-water interfaces
Innovations :Extension and application of the SCFT to handle
monolayers of branched lipids at air/water interfaces
Capacity :Analyse mesophases in surfactants ; identify function of their components
[ Y. Lauw, A. Kovalenko, and M. Stepanova, J. Phys. Chem. B 112 (2008) 2119;K.P. Santo, A. Kovalenko and M. Stepanova (2008) to be submitted ]
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Nano-Phase Domains in Lung Surfactants
B. Piknova et. al., Curr..Opinion in Struct. Biol. 12 (2002)487
Phase separation in compressed DPPC filmAdapted from [A. Cruz et. al. Langmuir, 21 (2005) 5349 ]
Dipalmitoylphosphatidylcholine(DPPC) is the most abundant component in lung surfactants
Surfactants cover the surface of lung alveoli.
These surfactants maintain low surface tension during breathing.
When compressed, membranes of liquid DPPCform micro- and nanodomains of gel phase.
This process may be basic for the lung' function.
But quantitative understanding of the kinetics is not available.
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Kinetic Modeling of Nanodomains in Monolayers of DPPC
Diffusionof DPPC
Driftby mean force
Excludedvolume
Filmcontinuity
Long-rangeattraction
A quantitative model imitates kinetics of a “breath-like” process when the surface area changes
EXAMPLES
Dark → gel (condensed)Light → liquid (expanded)
DPPC phase-separates spontaneously
100 nm
0.05 ms 0.5 ms 5 ms
Equilibration 2 ms
The morphology change is reversible Morphology is dramatically area-dependent
10% 15% 15%
Total area of gel nanodomains equilibrates over a few ms, e.g. is highly efficient for maintaining low surface tension in lungs.
The size of gel nanodomains tends to increase slowly, and is kinetically limited.Micron-scale domains may arise from fluctuations in area density of DPPC molecules.
Area reduction:
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Structure-Function Relation in Proteins
http://farm2.static.flickr.com
Proteins are necessaryfor virtually every activity in cells
http://photos.signonsandiego.comThey are alsothe most variableand complex molecules
http://astrojan/protein1.jpg
General rules behind proteins folding structure,which define their function(or dysfunction)remain largely unknown
Molecular Dynamics Modelingrepresents molecular motion in atomic detail
All atoms in protein Analysis of structure
Raw MD data are highly redundant and unsortedNeed extracting a manageable number of representative characteristics
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...for protein conformations ?
We develop advanced numeric methodsto characterize structural properties
of proteins
Image adapted fromhttp://blog.wired.com/gadgets/shower-elemental.jpg
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1. MD trajectorygenerated
~0.1 ns
2. Essentialcollective coordinates
identified
3. Generalized Langevin equations (GLE)
derived
4. Dynamic structural domains
identified
Framework :Modeling of Coarse-Grained Dynamics in Proteins
Background :Essential coordinates: A. Kitao, F. Hirata, and N. Go, Chem. Phys. 158 (1991) 447
Mori projection method: H. Mori, Prog. Theor. Phys. 33, 423 (1965); ibid, Prog. Theor. Phys. 34, 399 (1965).
Innovations :Rigorous definition of the essential variables in GLE for proteins
Definition of dynamic domains and chain flexibility from direction cosines of principal components
Reference-free identification of structural subunits in proteins
[ M. Stepanova, Phys. Rev. E 76 (2007) 051918; Condens. Matter Phys. 10 (2007) 441 ]
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The domains indicate regionsof relative rigidity in the molecule
Off-domain regions are relatively soft
3 largest domains in protein G
Example: Dynamic domains in protein GProtein G is often used to bind, detect, and/or characterize antibodies
Well-studied protein with known structure
Classic "benchmark" molecule for structural analysis
Colors indicate large domains
The domains identify compact groups of atomsalthough the spatial proximity is not required by the technique
There is a close ( but not a 100% )match with secondary structure
Gromacs 3.2.1 trajectory provided by Mark Berjanskii (2006)
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The predicted domain system in protein Gmatches NMR experiments
Adapted from [ M.J. Stone et. al., JACS., 123 (2001) 185 ]
Large domains correspond to high levels of model-free order parameter S2
The dynamic domain analysiscan be employed to interpret NMR data
Colorsindicatelarge domains
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Unfolding and misfolding of prion proteinsis the anticipated reason behind the prion diseases
The mechanism of unfolding/misfoldingis not understood clearly enough
Study of Structural Domains and Main-Chain Flexibility of Prion Proteins
Collaboration Dr. D. Wishart
The dynamic domain analysis may be indicative of the route of unfolding
[ N. Blinov, M. Berjanskii, D. Wishart, and M. Stepanova (2008), submitted ]
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OutlookOutlookBasic Studies
Structure of biomembranesand function of their components
Folding and dynamic structure of proteins
Applications: Environment
Exposure and toxic impact of nanoparticles
Applications:Biotechnologies
Detergents, foams, soaps, etc.,Protein engineering,
Drug discovery,Bioinformatics,
and more...
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Contact : Maria Stepanova, PhD, Dr.Sci.
National Institute for Nanotechnology NRC11421 Saskatchewan Drive,
Edmonton (AB) T6G 2M9Tel.: 1-780-641-1717
E-mail: [email protected]