An Introduction to Bioinformatics Protein Structure Prediction

An Introduction to Bioinformatics

• Protein Structure Prediction

Introduction

• Structure has several levels

• 1 primary
• 2 secondary
• 3 tertiary
• 4 quaternary

1 primary

• Amino acid sequence

2 secondary

• Localized organisation -helices and -sheets

3 tertiary

• Three-dimensional organisation

4 quaternary

• Multi protein assembly

The problem…..

Signal peptides

• Short N-terminal amino acid sequences

• Direct to membrane

• Cleaved after translocation

• SignalP

• Nobel Prize 1999 Günter Blobel

Intracellular targeting

• TargetP

• Predict subcellular location of eukaryotic protein

• Presequences

• Chloroplasts
• Mitochondria
• signal peptide

Transmembrane Domains

• Lots of programs

• TMHMM

• -helices
• hydrophobic  
• helix topology
• R or K +ve charge cytoplasmic side
• Hidden Markov Modelling

-helices and -sheets

-helices and -sheets

Super-secondary Structure

• Secondary structure elements combined into specific geometric arrangements known as motifs

Super-secondary Structure

• Several programs/websites for specific domains e.g.

• PAIRCOIL and MULTICOIL - detect coiled-coiled regions

• regions separating domains

• TRESPASSER - detects Leucine Zippers

• Leu-X6-Leu-X6-Leu-X6-Leu protein interaction domain

• NPS@nalysis Helix-Turn-Helix

• Protein interaction/DNA binding

Integrated stucture prediction

• One stop shop!

• Predict Protein at EBI

• secondary structure
• solvent accessibility globular regions
• transmembrane helices coiled-coil regions
• a multiple sequence alignment ProSite sequence motifs
• low-complexity retions
• ProDom domain assignments

Tertiary Structure Prediction

• Homology modelling

• Fold recognition

• Threading

• Model building

Homology Modelling

• Method of choice following BLAST search

• SWISS Model is a good WWW Interface

Homology Modelling

Homology Modelling

What if I have no homologue?