Modelling proteomesAn integrated computational framework for systems biology research

Ram SamudralaUniversity of Washington

How does the genome of an organism specify its behaviour and characteristics?

Proteome – all proteins of a particular system

~60,000 in human

~60,000 in rice

~4500 in bacterialike Salmonella andE. coli

Several thousanddistinct sequencefamilies

Modelling proteomes – understand the structure of individual proteins

A few thousanddistinct structuralfolds

Modelling proteomes – understand their individual functions

Thousands ofpossible functions

Modelling proteomes – understand their expression

Different expressionpatterns based ontime and location

Modelling proteomes – understand their interactions

Interactions andexpression patternsare interdependentwith structure andfunction

CASP6 prediction (model1) for T02155.0 Å Cα RMSD for all 53 residues

Ling-Hong Hung/Shing-Chung Ngan

Ling-Hong Hung/Shing-Chung Ngan

CASP6 prediction (model1) for T02814.3 Å Cα RMSD for all 70 residues

Tianyun Liu

CASP6 prediction (model1) for T02311.3 Å Cα RMSD for all 137 residues (80% ID)

CASP6 prediction (model1) for T02712.4 Å Cα RMSD for all 142 residues (46% ID)

Tianyun Liu

Prediction of HIV-1 protease-inhibitor binding energies with MD

Ekachai Jenwitheesuk

Can predict resistance/susceptibility to six FDA approved inhibitors with 95% accuracy in conjunction with knowledge-based methods

http://protinfo.compbio.washington.edu/pirspred/

Prediction of protein interaction networks

Jason McDermott

Interacting protein database

protein a

protein b

experimentallydeterminedinteraction

Target proteome

protein A85%

predictedinteraction

protein B90%

Assign confidence based on similarity and strength of interaction

Key paradigm is the use of homology to transfer informationacross organisms; not limited to yeast, fly, and worm

Consensus of interactions helps with confidence assignments

E. coli predicted protein interaction network

Jason McDermott

M. tuberculosis predicted protein interaction network

Jason McDermott

C. elegans predicted protein interaction network

Jason McDermott

H. sapiens predicted protein interaction network

Jason McDermott

Network-based annotation for C. elegans

Jason McDermott

Jason McDermottArticulation point proteins

Identifying key proteins on the anthrax predicted network

Jason McDermott

Identification of virulence factors

Bioverse – explore relationships among molecules and systems

Jason McDermott/Michal Guerquin/Zach Frazier

http://bioverse.compbio.washington.edu

Bioverse – explore relationships among molecules and systems

Jason McDermott/Michal Guerquin/Zach Frazier

http://bioverse.compbio.washington.edu

Bioverse – explore relationships among molecules and systems

Jason McDermott/Michal Guerquin/Zach Frazier

http://bioverse.compbio.washington.edu

Bioverse – explore relationships among molecules and systems

Jason McDermott/Michal Guerquin/Zach Frazier

http://bioverse.compbio.washington.edu

Bioverse - Integrator

Aaron Chang

Take home message

Prediction of protein structure, function, and networks may be used to model whole genomes to

understand organismal function and evolution

Where is all this going?

Structuralgenomics

Functionalgenomics

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Computationalbiology

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Acknowledgements

Aaron ChangChuck MaderDavid NickleEkachai JenwitheesukGong ChengJason McDermottKai Wang

Ling-Hong HungMike InouyeMichal GuerquinStewart MoughonShing-Chung NganTianyun LiuZach Frazier

National Institutes of HealthNational Science Foundation

Searle Scholars Program (Kinship Foundation)UW Advanced Technology Initiative in Infectious Diseases

http://bioverse.compbio.washington.eduhttp://protinfo.compbio.washington.edu