Self Organization in Biomolecular Systems Simulating the folding and aggregation of peptides proteins and lipids. Alan E. Mark School of Molecular Microbial Sciences Making Simulation of Biomolecular Systems Match Reality Alan E. Mark School of Molecular Microbial Sciences Simulating the folding and aggregation of peptides proteins and lipids. Periodic Boundary Conditions water Molecular Dynamics A molecular force field describing the inter-atomic interactions (underlying model) Solve Newtons equations of motion Time evolution of the system (classical mechanics) Self Organization in Biomolecular Systems Simulating the folding and aggregation of peptides proteins and lipids. Thermodynamic Properties of Biomolecules Free energy calculations, ligand design, force field refinement. Protein Structure Prediction and Refinement Structural Proteomics. Non-equilibrium protein dynamics Signal transduction, cell surface receptors, mechanoselective pores. 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 Factors that Determine Reliability 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? To Match Reality Folding and aggregation of peptides and proteins. Self Organization in Biomolecular Systems 1. Beta- peptides Betanova EPO VPAL Acknowledgements Folding and aggregation of peptides and proteins. Self Organization in Biomolecular Systems 2. - Peptides helical peptides Coiled Coils WW domain Beta-peptide Rep-exchange Acknowledgements SIV gp32 Acknowledgements Folding and aggregation of peptides and proteins. Self Organization in Biomolecular Systems 3. SUP 35 SH3 transition states Acknowledgements Folding and aggregation of peptides and proteins. Self Organization in Biomolecular Systems 4. Folding rates Spontaneous Aggregation of Lipids and Surfactant Systems Self Organization in Biomolecular Systems 5. Vesicle Formation Bilayer Formation Vesicle Fusion Phase Transition CC Domain Formation Phase Transition AA Acknowledgements Isoprene Resorcinol Spontaneous Aggregation of Membrane Protein Systems Self Organization in Biomolecular Systems 6. Peptide Pores Equ II W112 Acknowledgements PYP Particle Migration TRAIL_DR5 TRAIL Non-equilibrium dynamics Signal transduction, cell surface receptors, mechanoselective pores. Protein Structure Prediction and Refinement MD Structure Refinement Acknowledgements Solvent Oscillation Chaperone Cage Folding of Hydrophobin Ronen Zangi Hari Leontiadou Marcel L. Vocht (Biomade) George Robillard (Biomade) Stability of Betanova Patricia Soto Danilo Roccatano (Rome) Giorgio Colombo (Milan) Luis Serrano (EMBL) Manuela Lopez de la Paz (EMBL) Spontaneous Aggregation of Lipids Siewert-Jan Marrink Alex de Vries Peter Tieleman (Calgary) Eric Lindahl (Sweden) Aggregation of EPO Gilles Pieffet Structure Refinement Fan Hao Ying Xu Activation of Death Receptor DR5 Tjserk Wassenaar Win Quax (RUG) Activation of Photoactive Yellow Protein Gerrit Groenhof Mike Rob (London) Thrombin Inhibitors Alessandra Villa Ronen Zangi Gilles Pieffet Field Induced Particle Migration Volker Knecht Siewert-Jan Marrink Jan Engberts (RUG) Activation of Dengue Virus Daniela Mller Bostjan Kobe Thorsten Kampmann Paul Young Aggregation of Amyloid Peptides Xavier Periole Aldo Ramponi Patrica Soto Mchele Vendruscolo (Cambridge) Spontaneous Pore formation Siewert-Jan Marrink Hari Leontiadou Durba Sengupta David Poger Major Funding GBB