Simulating Protein Folding

1. Simulating Protein Folding - Some Ideas Christian Hedegaard Jensen Dmitry Nerukh

2. Outline • Introduction • Transition Matrix • Wang-Landau

3. Outline • Introduction • Transition Matrix • Wang-Landau

4. Introduction • We are simulation protein folding using Molecular Dynamics, and understanding using complexity analysis. • Try to do statistics on trajectories, to see if there are any patterns in where they go. (Transition Matrix) • Try and look at the paths that a protein can take when it folds. (Wang-Landau)

5. Outline • Introduction • Transition Matrix • Wang-Landau

6. Transition Matrix • Find states in trajectory • Find transitions between states in trajectory • Write up transition matrix for system • Possibly include some memory into the system.

7. Transition Matrix

8. Transition Matrix

9. Transition Matrix • We have a molecular dynamics simulation of a tripeptide. • Trianaline • 300 K, 1 atm • 12 ps (2fs) • OPLSAA-2001 force field • GROMACS

10. Transition Matrix Ramachandran Plot

11. Transition Matrix

12. Transition Matrix

13. Transition Matrix • Gives useful information about what is going on in the system. • Find out where we end and with what probabilities. • Look at transitions between clusters of states.

14. Outline • Introduction • Transition Matrix • Wang-Landau

15. Wang-Landau • Wang-Landau simulations, using a combination of Molecular Dynamics and Monte Carlo.

16. Wang-Landau • Wang-Landau gives the (relative) density of states. • The dos of a simple protein was obtained, d(E). • Try to calculate d(,E) or d(, ,E) .

17. dos q 0 2p Wang-Landau

18. Wang-Landau • Define reaction coordinates • Sample as function of these coordinates • Method does not say what the system does, but is says what is possible.

19. Wang-Landau • Matlab

20. Thank you!