Transcript DNA, The holy grail of bio-simulation - Fabien Fontaine

From dynamics to structure and function of model
bio-molecular systems
Presentation by Fabien Fontaine-Vive
&
Thesis supervisors:
Mark Johnson (Institut Laue-Langevin, Grenoble, France )
Gordon Kearley (University of Technology, Delft)
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Defense ceremony, April 24, 2007
Goal: extending recent work on dynamics of hydrogen bonded crystals to biopolymers
simulation vs. experiments, dynamics as a structural probe
Short strong
hydrogen bond crystals
=> 100-150 atoms
Secondary structures of proteins
Hydrated protein
with triple helices
=>100-150 atoms
=> 350 atoms
Explained proton transfer
with temperature
DNA, the holy grail
of bio-simulation
Validation of methods on
different types (strength,
length) of hydrogen bond
=> 4000 atoms !
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Methods
Why studying dynamics ?
Knowledge of the structure is difficult to obtain (semi-crystalline
and amorphous systems) and not sufficient
Why with neutrons ?
Neutron scattering of biological system is very sensitive to hydrogen
diffusion factor
Why ab-initio simulations ?
“Parameter-free”, only the electronic configuration of elements and
not refinement of a lot of spring constants modeling the polymer chain
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Amide group, amide bands
sheet
helix
I: C=O stretch + N-H in-plane bend
II: N-H in-plane bend + C-N stretch
III: C-N stretch + N-H in-plane bend
V: N-H out-of-plane bend + C-N torsion
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Kevlar, poylproline and polyglycine,
Secondary structures of proteins
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Sheets packing: amide V band of Kevlar, new structure
Semi-crystalline structure
Relative orientation of amide groups
Relative orientation of phenyl rings
Neutron diffraction & DFT-optimised structures
 no parallel packing of phenyl rings
 packing of amide groups impossible to distinguish
 probing the local structure with INS
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S(Q,w) ~ Σ σ.(Q.u).eiQ.r
σ: atomic diffusion factor
u: vector of displacement
Relative orientation of amide
groups
N
Amide V
H
DFT link, structure-dynamics (INS)
=> new sheets packing of Liu
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Sheet vs. helix dynamics: amide I band of polyglycine
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Polyglycine II
Polyglycine-I (beta-sheets)
S(Q,w) [arb.units]
-experimental data
- DFT normal modes
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Polyglycine-II (helices)
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Frequency (wavenumber)
sheets
helices
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Collagen,
a model for protein with triple helices
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* Collagen is the fibrous protein constituent skin, cartilage
bone and other connective tissues
*It is constituted by three chains of amino acids of proline
and glycine wound together in a tight triple helix.
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Hydrated collagen (r.h. 6%)
Interhelices hydrogen bond
First hydration shell, structural water
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Vibrational properties, amide bands
Amide bands
Vibrational signature of the tertiary structure formation
S(Q,w) of hydrated collagen
(6% of relative humidity) at low temperature
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DNA,
The holy grail of bio-simulation
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An atomistic model of DNA (random sequence)
An atomistic model of B-DNA (random sequence)
1000 water molecules, 10 base pairs, optimized with Force Fields
>10000 normal modes, >2000 in the range [0-100] cm-1
=> Need a bead representation
Selected eigenvectors,
in a bead representation
Breathing mode at 100 cm-1
involved in base-pair opening
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Making films of oriented DNA fibers
DNA film
X-ray pattern
scattering intensity (u.a.)
oriented DNA
Spinning apparatus
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energy transfer (cm-1)
INS experiment
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Messages for future work
Clear evidence of a strong link between structure and dynamics with DFT (parameter-free!)
for biopolymers (proton transfer, amide bands)
The numerical precision of DFT needs to be increased to handle low frequency excitations
in amorphous systems (normal modes vs. molecular dynamics of hydrated collagen)
Collagen (~350 atoms, CPU time for 2 ps of DFT-MD simulation = 1 month !)
=> Order N or QM/MM or FF methods to treat hydrated DNA (DFT~4N)
Dynamical signature of humidity-driven structural transitions. The B form of DNA turns into
the A-form on drying.
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