1. 1 Molecular Simulation 黃鎮剛 交通大學 生物科技系及生物資訊所

2. 2 Empirical Force Field http://life.nctu.edu.tw/~jkhwang/molsim

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4. 4 Free software VMD & NAMD  Molecular Dynamics, Graphics (OpenGL) SwissPDB Viewer  Minimization, Modeling, Graphics (OpenGL) Cn3D  Strutcure alignment, Graphics (OpenGL) Rasmol  Graphics (2D)

5. 5 Warming up Let's take a look at VMD

6. 6 Molecular Simulation Jump Start Quick Start

7. 7 A simple empirical force field

8. 8 Analysis of molecular topology Bonded interactions  The number of bonds 1-2 interactions  The number of angles 1-3 interactions  The number of torsions 1-4 interactions Non-bonded interactions  Van der Waals and electrostatic interactions The nunmber of nonbonded interactions

9. 9 ?? bonds ?? angle terms ?? torsional terms ?? non-bonded interactions

10. 10 ?? bonds ?? angle terms ?? torsional terms ?? non-bonded interactions How many types of bonds?

11. 11 ?? bonds ?? angle terms ?? torsional terms ?? non-bonded interactions How many types of bonds? C-C C-H

12. 12 ?? bonds ?? angle terms ?? torsional terms ?? non-bonded interactions How many types of bonds? C-C 2 C-H 8

13. 13 10 bonds ?? angle terms ?? torsional terms ?? non-bonded interactions How many types of bonds? C-C 2 C-H 8

14. 14 10 bonds ?? angle terms ?? torsional terms ?? non-bonded interactions How many types of angles?

15. 15 10 bonds ?? angle terms ?? torsional terms ?? non-bonded interactions C-C-C C-C-H H-C-H How many types of angles?

16. 16 10 bonds ?? angle terms ?? torsional terms ?? non-bonded interactions C-C-C 1 C-C-H 10 H-C-H 7 How many types of angles?

17. 17 10 bonds 18 angle terms ?? torsional terms ?? non-bonded interactions C-C-C 1 C-C-H 10 H-C-H 7 How many types of angles?

18. 18 10 bonds 18 angle terms ?? torsional terms ?? non-bonded interactions How many types of torsions?

19. 19 10 bonds 18 angle terms ?? torsional terms ?? non-bonded interactions How many types of torsions? H-C-C-H H-C-C-C

20. 20 10 bonds 18 angle terms 18 torsional terms ?? non-bonded interactions How many types of torsions? H-C-C-H 12 H-C-C-C 6

21. 21 10 bonds 18 angle terms 18 torsional terms ?? non-bonded interactions How many types of nonbonded ineractions?

22. 22 10 bonds 18 angle terms 18 torsional terms ?? non-bonded interactions How many types of nonbonded ineractions? H-H C-C

23. 23 10 bonds 18 angle terms 18 torsional terms 27 non-bonded interactions How many types of nonbonded ineractions? H-H 21 C-C 6

24. 24 Force field parameters Transferability  A C-H is a C-H, no matter where it occurs.  Force fields are empirical, there is no so- called "correct" form for a force field.  The form of force field is a compromise between "accuracy" and "computational efficiency".

25. 25 Atom types  Contains information about hybridization and sometimes the local environment.  sp 3, sp 2, sp  The reference angles is 109.5 for sp 3 carbon and 110 for sp 2 carbon

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27. 27

28. 28 Bond stretching Morse potential Harmonic potential

29. 29 C_04H_01250.0 1.090 C_04C_04250.0 1.523 C_04C_03250.0 1.534 C_04N_03 250.0 1.470 C_04N_04 200.0 1.430 C_04O_01 200.0 1.430 C_03C_03 500.0 1.393 C_03H_01 50.00 1.024 C_03N_03 500.0 1.324 C_03 N_04500.0 1.339 C_03O_00 500.0 1.235 C_03O_01 500.0 1.460 C_04 S_02 250.0 1.789 N_03 H_01 250.0 1.040 N_04 H_01 250.0 1.039 O_01 H_01 252.0 0.970 S_02 H_01 250.0 1.000 K in kcal/mol/A 2

30. 30 C_04H_01250.0 1.090 C_04C_04250.0 1.523 C_04C_03250.0 1.534 C_04N_03 250.0 1.470 C_04N_04 200.0 1.430 C_04O_01 200.0 1.430 C_03C_03 500.0 1.393 C_03H_01 50.00 1.024 C_03N_03 500.0 1.324 C_03 N_04500.0 1.339 C_03O_00 500.0 1.235 C_03O_01 500.0 1.460 C_04 S_02 250.0 1.789 N_03 H_01 250.0 1.040 N_04 H_01 250.0 1.039 O_01 H_01 252.0 0.970 S_02 H_01 250.0 1.000 K in kcal/mol/A 2

31. 31 H_01 C_04 H_01 60.0 109.2 H_01 C_04 O_01 60.0 109.2 C_04 C_04 C_04 60.0 111.1 C_04 C_04 H_01 60.0 109.2 C_04 C_04 N_03 60.0 108.2 C_04 C_04 O_01 60.0 109.8 C_03 C_04 C_04 60.0 109.8 C_03 C_04 H_01 60.0 109.2 C_03 C_04 N_03 60.0 112.3 C_03 C_04 O_01 60.0 110.0 N_04 C_04 C_04 60.0 110.9 N_04 C_04 H_01 60.0 109.2 N_03 C_04 H_01 60.0 108.2 N_03 C_04 N_03 120.0 120.0 H_01 C_03 H_01 40.0 120.0 N_03 C_03 O_00 120.0 123.1 N_04 C_03 N_04 120.0 119.9 O_00 C_03 H_01 120.0 119.9 O_01 C_03 O_00 120.0 122.3 C_04 C_03 H_01 60.0 119.2 C_04 C_03 N_03 60.0 117.5 C_04 C_03 O_00 60.0 119.2 C_04 C_03 O_01 60.0 119.2 K in kcal/mol C_03 C_03 C_04 120.0 120.0 C_03 C_03 C_03 120.0 119.9 C_03 C_03 H_01 60.0 120.0 C_03 N_04 C_04 60.0 124.0 C_03 N_04 H_01 60.0 120.0 C_04 N_04 H_01 60.0 109.9 H_01 N_04 H_01 60.0 120.0 H_01 N_03 H_01 60.0 113.9 C_04 N_03 C_04 60.0 110.6 C_04 N_03 H_01 60.0 113.0 C_03 N_03 C_04 60.0 120.9 C_03 N_03 H_01 60.0 120.4 Lp__ N_03 Lp__ 50.0 130.0 Lp__ N_03 H_01 50.0 109.0 Lp__ N_03 C_04 50.0 109.0 C_03 O_01 H_01 60.0 120.0 C_03 O_01 H_01 40.0 120.0 C_04 O_01 H_01 60.0 120.9 C_04 O_01 C_04 50.0 119.0 H_01 O_01 H_01 50.0 110.0 Lp__ O_01 Lp__ 50.0 130.0 Lp__ O_01 H_01 50.0 109.0 Lp__ O_01 C_04 50.0 109.0 Lp__ O_01 C_03 50.0 120.0

32. 32 C_04C_041.403 0.0 C_04C_030.002 180.0 C_04O_010.603 0.0 C_03 C_03 10.002 180.0 C_03 C_00 10.00 2 180.0 C_03 H_01 10.00 2 180.0 C_03 N_03 7.50 2 180.0 C_03 O_00 0.00 1 0.0 C_03 O_01 0.00 1 0.0 H_01N_03 7.50 2 180.0 N_03 C_04 0.00 3 0.0 N_04 C_04 1.40 3 0.0 N_04 C_03 10.00 2 180.0 N_04 H_01 7.50 2 180.0 S_02 C_04 1.00 3 0.0 S_02 C_03 0.00 3 0.0 S_02 S_02 6.00 2 0.0

33. 33 C_04C_041.403 0.0 C_04C_030.002 180.0 C_04O_010.603 0.0 C_03 C_03 10.002 180.0 C_03 C_00 10.00 2 180.0 C_03 H_01 10.00 2 180.0 C_03 N_03 7.50 2 180.0 C_03 O_00 0.00 1 0.0 C_03 O_01 0.00 1 0.0 H_01N_03 7.50 2 180.0 N_03 C_04 0.00 3 0.0 N_04 C_04 1.40 3 0.0 N_04 C_03 10.00 2 180.0 N_04 H_01 7.50 2 180.0 S_02 C_04 1.00 3 0.0 S_02 C_03 0.00 3 0.0 S_02 S_02 6.00 2 0.0 The parameters depend only on 2,3 atoms

34. 34

35. 35

36. 36

37. 37

38. 38 Improper torsional angles

39. 39 Improper torsional angles 1 2 34

40. 40 Improper torsional angles 1 2 34

41. 41 Atom r o  C_031.753.92020.0376 C_04 1.85 3.91500.0738 H_01 1.10 2.65250.0010 N_03 1.65 3.21710.4132 O_00 1.60 3.20050.1848 O_01 1.60 3.20050.1848 S_02 1.85 3.91500.0738 Lp__ 1.10 2.6525 0.0010

42. 42 Cross-term interactions

43. 43 Cross terms Stretch-stretch Stretch-torsion Stretch-bend Bend-torsion Bend-bend These terms are important for vibrational frequency prediction.

44. 44 Staggering effect

45. 45 Staggering effect Carbon: +1 Lone electron -1/2

46. 46 Polarization

47. 47 Polarization Approximation Electrostatic field does not include contributions from atom i

48. 48 Polarization New model H H O

49. 49 Polarization is computational intensive Its effects is important in the simulation of ionic solution. The system usually contains atom or ions and small molecules.

50. 50 Solvent dielectric models Effetive dielectric constant

51. 51 Hydrogen bonds Hydrogen bond is of electrostatic nature. No special term for hydrogen bonds Or 10-12 potential  is the angle formed by A…H-D

52. 52 Water models SPC, SPC/E, TIP3P TIP4P, BF ST2