1. SMA5233 Particle Methods and Molecular Dynamics Lecture 6: Coarse-grained hybrid MD A/P Chen Yu Zong Tel: 6516-6877 Email: phacyz@nus.edu.sg http://bidd.nus.edu.sg Room 08-14, level 8, S16 National University of Singapore phacyz@nus.edu.sg http://bidd.nus.edu.sgphacyz@nus.edu.sg http://bidd.nus.edu.sg

2. 2 Flow Chart For a Typical MD Program Initialize Variables Build Model Define Material Start Integrate Set Boundary Conditions End Define the positions of the atoms Assign randomly generated velocities Initialize Variables

3. 3 Flow Chart For a Typical MD Program Initialize Variables Build Model Define Material Start Integrate Set Boundary Conditions End Define the simulation domain Build atoms to lattice Build Model

4. 4 Flow Chart For a Typical MD Program Initialize Variables Build Model Define Material Start Integrate Set Boundary Conditions End Specify interatomic potentials Define Material

5. 5 Flow Chart For a Typical MD Program Initialize Variables Build Model Define Material Start Integrate Set Boundary Conditions End Set initial temperature distribution Specify thermodynamic controls Set Boundary Conditions

6. 6 Flow Chart For a Typical MD Program Initialize Variables Build Model Define Material Start Integrate Set Boundary Conditions End Compute the forces at time=0 Set frequency of outputs Start

7. 7 Flow Chart For a Typical MD Program Initialize Variables Build Model Define Material Start Integrate Set Boundary Conditions End Compute the atomic trajectories Compute other desired outputs Integrate

8. 8 Flow Chart For a Typical MD Program Initialize Variables Build Model Define Material Start Integrate Set Boundary Conditions End Compute final thermodynamic outputs Calculate program statistics End

9. 9 Fully Atomistic Simulations Computation of material properties based on explicit treatment of atomic degrees of freedom Computationally expensive Too many degrees of freedom Only capable on small DNA duplexes Time duration in nanoseconds Limitations

10. 10 Coarse-grained Model DNA Sugar and Phosphate groups reduced to one molecule(bead) Each DNA base is represented by one molecule(bead) Fully Atomistic Model Coarse-grained Model

11. 11 Advantages of the Coarse-grained Model Computationally less expensive Decreases degrees of freedom Coarse-grained model DNA duplex  Allows for longer DNA duplexes  Time length up to microsecond Chemical structure of DNA duplex

12. 12 Coarse-grained Model One or multiple amino acids reduced to one molecule(bead)

13. Intra-Polymer Forces – Combinations Of the Following: Stiff (Fraenkel) / Hookean Spring Lennard-Jones Repulsion Finitely-Extensible Non-linear Elastic (FENE) Spring

14. Intra-Polymer Forces – Combinations Of the Following: Lennard-Jones Repulsion Finitely-Extensible Non-linear Elastic (FENE) Spring

15. Intra-Polymer Forces (continued) Stiff: Schlijper, Hoogerbrugge, Manke, 1995 Hookean + Lennard-Jones: Nikunen, Karttunen, Vattulainen, 2003 FENE: Chen, Phan-Thien, Fan, Khoo, 2004 Marko-Siggia WormLike Chain Can be adjusted if M>2 (Underhill, Doyle 2004)

16. 16 An Example

17. 17 An Example

18. 18 An Example

19. 19 An Example

20. 20 An Example

21. 21 An Example

22. 22 An Example

23. 23 An Example

24. 24 An Example

25. 25 A Case Study

26. 26 A Case Study

27. 27 A Case Study

28. 28 A Case Study