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From dynamics to structure and function of model bio-molecular systems

Presentation by Fabien Fontaine-Vive

Defense ceremony, April 24, 2007

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Thesis supervisors:

Mark Johnson (Institut Laue-Langevin, Grenoble, France )Gordon Kearley (University of Technology, Delft)

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Goal: extending recent work on dynamics of hydrogen bonded crystals to biopolymers

DNA, the holy grail of bio-simulation

=> 4000 atoms !

Explained proton transfer with temperature

Validation of methods on different types (strength, length) of hydrogen bond

Short strong hydrogen bond crystals

=> 100-150 atomsSecondary structures of

proteins

=>100-150 atoms

Hydrated protein with triple helices

=> 350 atoms

simulation vs. experiments, dynamics as a structural probe

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Methods

Why studying dynamics ? Knowledge of the structure is difficult to obtain (semi-

crystallineand amorphous systems) and not sufficient

Why with neutrons ?Neutron scattering of biological system is very sensitive to

hydrogendiffusion 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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I: C=O stretch + N-H in-plane bendII: N-H in-plane bend + C-N stretchIII: C-N stretch + N-H in-plane bendV: N-H out-of-plane bend + C-N torsion

Amide group, amide bands

sheet

helix

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Kevlar, poylproline and polyglycine,

Secondary structures of proteins

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Relative orientation of amide groupsRelative 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

Semi-crystalline structure

Sheets packing: amide V band of Kevlar, new structure

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Relative orientation of amide groups

DFT link, structure-dynamics (INS)=> new sheets packing of Liu

HN

Amide V

S(Q,w) ~ Σ σ.(Q.u).eiQ.r

σ: atomic diffusion factoru: vector of displacement

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Polyglycine-II (helices)

Sheet vs. helix dynamics: amide I band of polyglycine

sheets

helices

Polyglycine-I (beta-sheets)

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Collagen,

a model for protein with triple helices

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* Collagen is the fibrous protein constituent skin, cartilagebone 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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S(Q,w) of hydrated collagen

(6% of relative humidity) at low temperature

Vibrational properties, amide bands

Amide bands

Vibrational signature of the tertiary structure formation

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DNA,

The holy grail of bio-simulation

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An atomistic model of DNA (random sequence)

Selected eigenvectors,in a bead representationBreathing mode at 100 cm-1involved in base-pair opening

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

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X-ray pattern

DNA film

Making films of oriented DNA fibers

INS experimentSpinning apparatus

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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.