Membrane Protein Structure Prediction and Visualization Chuck Staben Jerzy Jaromczyk

Genbank Growth

GenomeTranscriptomeProtein Genomic View Structures Processes Cell Environment

Protein Structure Determination

Bioinformatics-what is it? Acquisition, curation, and analysis of biological data Hypothesis

Typical Cell ~10% proteins membrane bound Up to 90% cell’s energy involved in transport Receptors, transporters, adhesion Basic and applied

Protein Structure Rasmol image 3D structure (tertiary) –Secondary structure Alpha helix Beta sheet PRIMARY STRUCTURE  3D Structure

Primary Structure 20 amino acids –Unique chemical properties ’s (400 typical)

Structure Prediction Quantum models Molecular dynamics Comparative--“Threading” Simple predictive –Eg. Chou-Fasman

Chou-Fasman, proteins (ALL soluble), determine relative tendencies of amino acids –P alpha, P beta … –“Rules” for prediction Does this sample represent proteins well? Prediction success compared to “newly solved”

Overall Success ~60% correct Membrane proteins –~30% correct!!!!

Membrane Protein Sample ~60 structures of “membrane” proteins –Some were soluble-only parts of larger ones –Redundancy/similarity –~20 DISTINCT proteins Vary in membrane localization DIFFERENT P-factors!!! –Statistically evaluated differences

Algorithm Adopt, essentially without reconsideration Code (several versions) –Up to 50% CORRECT readily

Visualization “Simple” problem –No obvious good solution Start simple –“beads on a string” –modular –Interactive –collaborative

Visualization Beads on a string Insertion

Interpretation Critical?