molmodel workshop
DESCRIPTION
Molmodel Workshop. March 21, 2008 Christopher Bruns. 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. What is Molmodel?. Domain-specific modeling layer on Simbody Part of SimTK core libraries - PowerPoint PPT PresentationTRANSCRIPT
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Molmodel Workshop
March 21, 2008Christopher Bruns
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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
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What is Molmodel?
• Domain-specific modeling layer on Simbody• Part of SimTK core libraries• You should have Programmer’s Guide
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SimTK Molmodel molecular modeling
SimTK Simbody order(n) multibodydynamics
SimTK Lapack linear algebra
SimTK Common Vector, Matrix classesand other data structures
SimTK Math numerical methodsand linear algebra
Principal SimTK Core Libraries
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Molecular Physical Units
• Length: nanometers (10-9 meters)• Time: picoseconds (10-12 seconds)• Mass: atomic mass units
(1/(Avogado’sConstant) grams)
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Argon
• Inert “noble” gas• Has no chemistry• van der Waals forces only
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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
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Biotype
• Bridge between structural model and force field implementation
• Concept borrowed from TINKER molecular dynamics package
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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
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Ethane
• Two carbons, six hydrogens• One dihedral degree of freedom• 3 kcal/mol energy barrier to rotation
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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
?
2 3
1
1 distance
bond angle 23 dihedral angle
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Molecule internal coordinates
• Bond lengths, bond angles, dihedral angles• Mandatory for Compound construction• Optional for Compound simulation
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Ethane Exercises
• Compile and run TwoEthanes example program
• Add a third ethane molecule
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Macromolecules, residues, and atoms
• RNA, DNA, and protein are large molecules called macromolecules
• Macromolecules consist of chains of residues
Atoms
Residues}Macromolecule
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Top level API for constructing proteins
#include “SimTKmolmodel.h”Protein(“ACDEFGHIKLMNPQRSTVWY”);
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Simple protein
• Construct protein from sequence• All atom parameters are built into AMBER99
force field• Note end caps
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Protein Exercises
• Compile and run SimpleProtein example program
• Try a different sequence• Add a second protein
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Simple RNA
• RNA from sequence• Writing PDB files
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RNA Exercises
• Compile and run SimpleRNA example program• Try a different sequence• Change the frequency of PDB writing
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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.
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Search box
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4-character ID
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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 22.00ATOM 1752 CA GLY C 250 32.365 1.086 41.969 1.00 21.39ATOM 1753 C GLY C 250 31.538 1.735 40.864 1.00 20.79ATOM 1754 O GLY C 250 30.621 2.527 41.152 1.00 21.58…
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LoadPdb Exercises
• Download 1AKG from Protein Data Bank http://www.rcsb.org/pdb
• Simulate 1AKG using Example
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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)
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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
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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
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Protein Internal Coordinates
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Nucleic Acid Internal Coordinates
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RigidProtein Exercises
• Simulate rigid protein• Create second protein• Convert to full Cartesian model• Which way is faster?
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Custom Molecule Construction
• BondCenters, Atoms, Bonds, Compounds• Inboard bond center• The first few atoms• Ring closing bonds
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Molecule Construction nomenclature1: Atoms(3)
3: Bonds(2)
2: BondCenters(9)
4: Compound(1)
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Submitting Bug Reports