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.
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