Protein structure prediction

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Protein structure prediction

• Anttu Kurttio
• Ville Pietiläinen

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Introduction

• Proteins are one of the most important parts in
  any biological systems.
• Understanding the folding of the amino-acid chain
  to produce functional proteins is essential for
  studying cellular systems.
• Fast and accessible methods of solving the 3D
  structure of a protein are in high demand.

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Protein structure

• This topic has been covered several times. Next! ?

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Computational methods

• Ab initio- methods
• Laws of physics amino-acid sequence protein
  structure
• Computes potential energy functions.
• Minimum potential energy is the most stable
  structure and as such the most likely.
• Computationally demanding.

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Comparative methods

• Based on the limited amount of possible tertiary
  structure types.
• Approximately 2000 different types of protein
  folds.
• Comparing the sample to a database of known
  structures, for example Protein Data Bank.

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Homology modelling

• Based on the assumption that homologous (related)
  proteins fold in a similar fashion.
• Folding is a highly conserved factor, much more
  so than amino-acid sequence.
• Finding a match between two distantly related
  proteins can be difficult.

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Protein threading

• Based on the assumption that similar folding has
  already been found.
• Comparing parts of the sequence to a database of
  known three dimensional structures using a
  scoring function.
• Works at least somewhat on approximately 80 of
  new protein sequences.

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Programs

• A lot of free programs are available.
• Server based programs do the computational work.
  For example Swiss-Model, Rosetta or PSIPRED.
• Downloadable applications are used for viewing
  the results. For example Swiss-PdbViewer or
  Rasmol.
• Distributed computing promises increases in
  computational capacity.

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DEMO

• Swiss-Model in four easy steps.
• swissmodel.expasy.org

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Step 1 Send in the sequence
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Step 2 Coffee break
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Step 3 Recieve mail
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Step 4 Open PDB-file
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Rejoice!

• Study your brand new model of a protein.
• ?