Self Organization in Biomolecular Systems

1. Self Organization in Biomolecular Systems Simulating the folding and aggregation of peptides proteins and lipids. Alan E. Mark School of Molecular Microbial Sciences a.e.mark@uq.edu.au

4. Periodic Boundary Conditions water

5. Molecular Dynamics A molecular force field describing the inter-atomic interactions (underlying model)

6. Solve Newton’s equations of motion Time evolution of the system (classical mechanics)

7. Thermodynamic Properties of Biomolecules Free energy calculations, ligand design, force field refinement. Self Organization in Biomolecular Systems Simulating the folding and aggregation of peptides proteins and lipids. Non-equilibrium protein dynamics Signal transduction, cell surface receptors, mechanoselective pores. Protein Structure Prediction and Refinement Structural Proteomics.

8. Factors that Determine Reliability • The Model (force field) • The model must encompass the property of interest • Time Scale. • The simulation time >> time scale of the process to be investigated

9. To Match Reality • The Model (force field) • Is the model fitted to the property of interest? • Time Scale. • Is the process spontaneous or enforced? • Know what is reality. • Are we fitting to just another model?

10. Self Organization in Biomolecular Systems 1. Folding and aggregation of peptides and proteins. Betanova Beta- peptides EPO VPAL Acknowledgements

11. Self Organization in Biomolecular Systems 2. Folding and aggregation of peptides and proteins. -Peptides helical peptides Coiled Coils WW domain Beta-peptide Rep-exchange Acknowledgements

12. Self Organization in Biomolecular Systems 3. Folding and aggregation of peptides and proteins. SUP 35 SIV gp32 Acknowledgements

13. Self Organization in Biomolecular Systems 4. Folding and aggregation of peptides and proteins. SH3 transition states Folding rates Acknowledgements

14. Self Organization in Biomolecular Systems 5. Spontaneous Aggregation of Lipids and Surfactant Systems Vesicle Formation Vesicle Fusion Bilayer Formation Phase Transition AA Phase Transition CC Domain Formation Resorcinol Isoprene Acknowledgements

15. Self Organization in Biomolecular Systems 6. Spontaneous Aggregation of Membrane Protein Systems Peptide Pores Equ II W112 Acknowledgements

16. Non-equilibrium dynamics Signal transduction, cell surface receptors, mechanoselective pores. TRAIL_DR5 TRAIL PYP Particle Migration Acknowledgements

17. Protein Structure Prediction and Refinement MD Structure Refinement Solvent Oscillation Chaperone Cage Acknowledgements

18. Folding of Hydrophobin Ronen Zangi Hari Leontiadou Marcel L. Vocht (Biomade) George Robillard (Biomade) Thrombin Inhibitors Alessandra Villa Ronen Zangi Gilles Pieffet Stability of Betanova Patricia Soto Danilo Roccatano (Rome) Giorgio Colombo (Milan) Luis Serrano (EMBL) Manuela Lopez de la Paz (EMBL) Aggregation of EPO Gilles Pieffet Spontaneous Aggregation of Lipids Siewert-Jan Marrink Alex de Vries Peter Tieleman (Calgary) Eric Lindahl (Sweden) Activation of Death Receptor DR5 Tjserk Wassenaar Win Quax (RUG) Aggregation of Amyloid Peptides Xavier Periole Aldo Ramponi Patrica Soto Mchele Vendruscolo (Cambridge) Field Induced Particle Migration Volker Knecht Siewert-Jan Marrink Jan Engberts (RUG) Structure Refinement Fan Hao Ying Xu Spontaneous Pore formation Siewert-Jan Marrink Hari Leontiadou Durba Sengupta David Poger Activation of Dengue Virus Daniela Müller Bostjan Kobe Thorsten Kampmann Paul Young Activation of Photoactive Yellow Protein Gerrit Groenhof Mike Rob (London)

19. Major Funding GBB