1. March 21, 2008 Christopher Bruns
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
SimTK Simbody
order(n) multibody
dynamics
SimTK Lapack
linear algebra
SimTK Common
Vector, Matrix classes
and other data structures
SimTK Math
numerical methods
and 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
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 N GLY C
ATOM CA GLY C
ATOM C GLY C
ATOM O GLY C

25. LoadPdb Exercises
Download 1AKG from Protein Data Bank
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