2008 Alberta Nanotech Showcaseadvancededucation.alberta.ca/media/179307/bioind_stepanova_nov20... · 2008 Alberta Nanotech Showcase November 20, 2008 ... Extension and application

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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0.2

0.4

0.6

0.8

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0 10 20 30 40 50 60 70 80

ϕ

z

WaterAir

Lipid tail

Lipid head

Con

cent

rati

on o

f Li

pid

Incr

ease

s

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]