1. 1 From dynamics to structure and function of model bio-molecular systems Presentation by Fabien Fontaine-Vive Defense ceremony, April 24, 2007 & Thesis supervisors: Mark Johnson (Institut Laue-Langevin, Grenoble, France ) Gordon Kearley (University of Technology, Delft)

2. 2 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 atoms Secondary structures of proteins =>100-150 atoms Hydrated protein with triple helices => 350 atoms simulation vs. experiments, dynamics as a structural probe

3. 3 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

4. 4 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 Amide group, amide bands sheet helix

5. 5 Kevlar, poylproline and polyglycine, Secondary structures of proteins

6. 6 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 Semi-crystalline structure Sheets packing: amide V band of Kevlar, new structure

7. 7 Relative orientation of amide groups DFT link, structure-dynamics (INS) => new sheets packing of Liu H N Amide V S(Q,w) ~ Σ σ.(Q.u).e iQ.r σ: atomic diffusion factor u: vector of displacement

8. 8 Polyglycine-II (helices) Sheet vs. helix dynamics: amide I band of polyglycine sheets helices Polyglycine-I (beta-sheets)

9. 9 Collagen, a model for protein with triple helices

10. 10 * 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.

11. 11 Hydrated collagen (r.h. 6%) Interhelices hydrogen bond First hydration shell, structural water

12. 12 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

13. 13 DNA, The holy grail of bio-simulation

14. 14 An atomistic model of DNA (random sequence) Selected eigenvectors, in a bead representation Breathing mode at 100 cm-1 involved 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

15. 15 X-ray pattern DNA film Making films of oriented DNA fibers INS experiment Spinning apparatus

16. 16 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.