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

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

2. 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 Hydrated protein with triple helices => 350 atoms Secondary structures of proteins =>100-150 atoms Explained proton transfer with temperatureValidation of methods on different types (strength, length) of hydrogen bond DNA, the holy grail of bio-simulation=> 4000 atoms !

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. Amide group, amide bands 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 sheet helix

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

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

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

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

9. Collagen,a model for protein with triple helices

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 glycinewound together in a tight triple helix.

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

12. 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

13. DNA,The holy grail of bio-simulation

14. 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

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

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.