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.