Molmodel Workshop

1. Molmodel Workshop March 21, 2008 Christopher Bruns

2. Schedule • 8:30-10:00 Molmodel examples • 10:00-10:15 Break • 10:15-11:30 More Molmodel examples • 11:30 Lunch • 12:00 Your projects

3. What is Molmodel? Domain-specific modeling layer on Simbody Part of SimTK core libraries You should have Programmer’s Guide

4. Principal SimTK Core Libraries SimTK Molmodel molecular modeling order(n) multibody dynamics SimTK Simbody numerical methods and linear algebra SimTK Math SimTK Common Vector, Matrix classes and other data structures SimTK Lapack linear algebra

5. Molecular Physical Units • Length: nanometers (10-9 meters) • Time: picoseconds (10-12 seconds) • Mass: atomic mass units (1/(Avogado’sConstant) grams)

6. Argon • Inert “noble” gas • Has no chemistry • van der Waals forces only

8. Molecular Force Field • What is a molecular force field? • A specification of all forces affecting a dynamic simulation. For conventional molecular simulation this includes non-bonded electrostatic forces and van der Waals forces, and bonded stretch, bend, torsion, and improper torsion parameters

9. Biotype Bridge between structural model and force field implementation Concept borrowed from TINKER molecular dynamics package

10. Argon Exercises Compile and run TwoArgons example program Add a third argon atom. What happens when atoms start too close together? Too far apart? Increase the attractive force between atoms ten-fold

11. Ethane • Two carbons, six hydrogens • One dihedral degree of freedom • 3 kcal/mol energy barrier to rotation

12. Internal coordinates • Instead of explicit Cartesian X, Y, Z coordinates for an atom • Given three other atom positions, one distance, one bond angle, and one dihedral angle 1 distance ? 1 3 dihedral angle bond angle 2 2 3

13. Molecule internal coordinates Bond lengths, bond angles, dihedral angles Mandatory for Compound construction Optional for Compound simulation

14. Ethane Exercises Compile and run TwoEthanes example program Add a third ethane molecule

15. Macromolecules, residues, and atoms • RNA, DNA, and protein are large molecules called macromolecules • Macromolecules consist of chains of residues } Macromolecule Atoms Residues

16. Top level API for constructing proteins #include “SimTKmolmodel.h” Protein(“ACDEFGHIKLMNPQRSTVWY”);

17. Simple protein • Construct protein from sequence • All atom parameters are built into AMBER99 force field • Note end caps

18. Protein Exercises Compile and run SimpleProtein example program Try a different sequence Add a second protein

19. Simple RNA • RNA from sequence • Writing PDB files

20. RNA Exercises Compile and run SimpleRNA example program Try a different sequence Change the frequency of PDB writing

21. PDB: The Protein Data Bank • http://www.rcsb.org/pdb/ • Repository of DNA, RNA, and protein atomic structures • Contains experimental results, not perfect models • Entries identified by 4 character ID, e.g. “1MRP”, “1GRZ” • Use “advanced search” at PDB web site to find structures.

22. Search box

23. 4-character ID

24. PDB File format • Text format – humans can read it too • Most of the information is atomic coordinates • PDB files usually contain multiple molecules, including water molecules … ATOM 1751 N GLY C 250 32.286 1.882 43.206 1.00 22.00 ATOM 1752 CA GLY C 250 32.365 1.086 41.969 1.00 21.39 ATOM 1753 C GLY C 250 31.538 1.735 40.864 1.00 20.79 ATOM 1754 O GLY C 250 30.621 2.527 41.152 1.00 21.58 …

25. LoadPdb Exercises Download 1AKG from Protein Data Bank http://www.rcsb.org/pdb Simulate 1AKG using Example

26. Coarse-grained representations in biology Natural lump sizes: • atoms • residues • base pairs • duplexes, alpha helices, beta strands • macromolecules • molecular assemblies • organelles • cells • tissues • organs • limbs • organisms • societies • ecosystems • biospheres • intergalactic federations (picometer to micron scale) (micron to mega-light-year scale)

27. Coarse-grained simulation of atom-based molecular models • Full atom force field • coarse-grained motion permits longer integration time steps • Increasing coarseness • full Cartesian • torsion only (internal coordinate) • full rigid

30. Molecule Mobility/Partitioning • What is molecule partitioning? • defining the movable degrees of freedom that will be used in a molecule simulation • Examples of partitioning strategies • Internal coordinates (fixed bond lengths and fixed bond angles) • Full Cartesian (conventional molecular dynamics) • Rigid molecules

31. Protein Internal Coordinates

32. Nucleic Acid Internal Coordinates

33. RigidProtein Exercises • Simulate rigid protein • Create second protein • Convert to full Cartesian model • Which way is faster?

34. Custom Molecule Construction • BondCenters, Atoms, Bonds, Compounds • Inboard bond center • The first few atoms • Ring closing bonds

35. Molecule Construction nomenclature 1: Atoms(3) 2: BondCenters(9) 3: Bonds(2) 4: Compound(1)

36. Submitting Bug Reports