Difference between revisions of "Canavan Task 8 - Molecular Dynamics Simulations"

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(Running Jobs)
(Intermediate steps)
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==Intermediate steps==
 
==Intermediate steps==
   
Simulation structure created!
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Simulation structure created!
 
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Water and box added!
 
Water and box added!

Revision as of 16:26, 2 July 2012

Protocol

Further information can be found in the protocol.


Choosing Mutants

We decided to use A305E and K213E for the MD analysis. In <xr id="CD_MD_mutants"/>.


<figtable id="CD_MD_mutants">

<xr nolink id="CD_MD_mutants"/> Description of the structural environment of each mutation and visualization of the pymol mutation and the scwrl mutation output.
Mutation Comment Visualisation
A305E A305 is located at the end of the 13th beta sheet at the C-terminus of the protein. In figure <xr nolink id="a305e_crowded"/> the mutated residue glutamic acid is shown in red. The space at this position is rather crowded, so that alanine as a small residue fits very well in this position. Glutamic acid instead, hardly finds space and overlaps with neighboring residues.
We decided to use this mutation, since we expect to see a huge effect in structure with the MD simulation.
<figure id="a305e_crowded">
<xr nolink id="a305e_crowded"/>
</figure>
K213E K213 is located on the loop connecting the N-, and C-terminal of the enzyme. It is on the surface of the protein, far away from the binding site or the dimer interaction site. In <xr nolink id="k213e_pymol"/>, the mutated residue K213E as computed by PyMol is presented in blue and the reference structure and residue in green. The mutated residue Glutamic Acid is able to form an HBond with the neighbouring helix. We chose this mutation since we do not expect to see any effect from this mutation. Also, our analysis so far suggests, that this mutation is not disease causing. Yet, it is annotated in the HGMD to cause Canavan Disease. We are curious about the MD outcome to either see the HGMD annotation confirmed or our predictions confirmed. <figure id="k213e_pymol">
<xr nolink id="k213e_pymol"/>
</figure>

</figtable>


Running Jobs

We had no problems to get the jobs started.

squeue -u di34fog --cluster mpp1

We started five jobs:

  • wt MD run with original 2O4H:A => Run time 05:22:45
  • K213E mutant based on Scwrl_min structure => Run time 05:19:05
  • K213E mutant based on Foldx_min structure => Run time 05:13:28
  • A305E mutant based on Scwrl_min structure => Run time 05:18:20
  • A305E mutant based on Foldx_min structure => Run time 05:13:28

Intermediate steps

 Simulation structure created!
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 Water and box added!
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 Ions added!
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 Number of chains 1
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 Number of atoms 45678
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 CHAIN 0: Protein
 Constraint files created
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 Run min I: solvent & fixed protein(SD)
 Solvent minimized!
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 Run min II: solvent & fixed backbone(SD)
 System minimized!
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 Run min III: solvent & fixed backbone(CG)
 System minimized!
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 Run NVT
 NVT finished!
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 Run NPT
 NPT finished!
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 Production run
 Running: step 2000000, remaining runtime:     0 s          
 Production run finished!