An analysis of the simplified normal modes of Ecotin

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An analysis of the simplified normal modes of
Ecotin

• Hugh Shanahan
• University College London
• October 2001

and here am i patiently squeezing four
dimensional ideas onto a two dimensional stage
e e cummings
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Outline

• Ecotin and panspecificity
• Model of interaction (Eggers et al.)
• Dynamics and normal mode analysis
• A simplified model
• Results
• Temperature factors
• Motions
• Conclusions

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Ecotin
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Simulation

• Molecular Dynamics (or Monte Carlo) is very very
  expensive
• Considers all (or at least many) possible degrees
  of freedom
• Never Clear when enough time steps (or
  configurations) is enough
• In this case we are not concerned with local
  atomic displacements
• Want large collective displacements

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And now for some scary Math..
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Difficulty with NMA

• The potential used is semi-empirical
• The original structure does not necessarily lie
  at a minimum for the full potential
• One has to minimise the energy of the structure
  before performing NMA
• May also have to deal with local minima

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Alright, but what exactly are you doing ??
Basically, take one of these.
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And just think about the C s...
a
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Now put springs between them.
And thats it !!!
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Results

• Can compute the temperature factors (the RMS
  variation of the atoms..)
• In test cases, the agreement is quite good...

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Ecotin Temperature Factors

• But in the case of Ecotin, the agreement is not
  so good.

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The possible range of structures from this
ensemble do not give the bound structure.
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Conclusions

• Motions are dominated by the two lowest
  eigenvalues, which are anti-symmetric.
• Motion between bound and unbound state is, on the
  other hand, symmetric.
• What is going wrong ?
• NMA tends to over amplify regions where
  Temperature factors have a peak, some correlation
  with accessibility.
• Model is in vacuum. Can include effect of water
  by introducing viscosity.

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Acknowledgements

• Advice and direction
• David Jones
• Janet Thornton
• Suggestions on the technical implementation
• Graham Smith (ICRF)
• Mark Williams