Protein structure prediction Anttu Kurttio Ville Pietiläinen.
Transcript of Protein structure prediction Anttu Kurttio Ville Pietiläinen.
Protein structure prediction
Anttu Kurttio
Ville Pietiläinen
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.
Protein structure
• This topic has been covered several times. Next!
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.
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.
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.
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.
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.
DEMO
• Swiss-Model in four easy steps.
swissmodel.expasy.org
Step 1: Send in the sequence
Step 2: Coffee break
Step 3: Recieve mail
Step 4: Open PDB-file
Rejoice!
• Study your brand new model of a protein.