View
215
Download
0
Category
Preview:
DESCRIPTION
FUNCTION Wang/Cheng Ion binding energy prediction with a correlation of 0.7 Calcium ions predicted to < 0.05 Å RMSD in 130 cases Meta-functional signature for DXS model from M. tuberculosis Meta-functional signature accuracy
Citation preview
MODELLING PROTEOMES
RAM SAMUDRALAASSOCIATE PROFESSOR
UNIVERSITY OF WASHINGTON
How does the genome of an organism specifyits behaviour and characteristics?
STRUCTURE
0.5 Å Cα RMSD for 173 residues (60% identity)
T0290 – peptidyl-prolyl isomerase from H. sapiens
T0364 – hypothetical from P. putida
5.3 Å Cα RMSD for 153 residues (11% identity)
T0332 – methyltransferase from H. sapiens
2.0 Å Cα RMSD for 159 residues (23% identity)
T0288 – PRKCA-binding from H. sapiens
2.2 Å Cα RMSD for 93 residues (25% identity)
Liu/Hong-Hung/Ngan
FUNCTION
Wang/Cheng
Ion binding energyprediction with a correlation of 0.7
Calcium ions predicted to < 0.05 Å RMSD
in 130 cases
Meta-functional signature for DXS model from M. tuberculosis
Meta-functional signatureaccuracy
INTERACTION
McDermott/Wichadakul/Staley/Horst/Manocheewa/Jenwitheesuk/Bernard
BtubA/BtubB interolog model from P. dejongeii(35% identity to eukaryotic tubulins)
Transcription factor bound to DNA promoter regulog model from S. cerevisiae
Prediction of binding energies of HIV protease mutants and inhibitors
using docking with dynamics
SYSTEMS
McDermott/Wichadakul
Example predicted protein interaction network from M. tuberculosis(107 proteins with 762 unique interactions)
In sum, we can predict functions for more than 50% of a proteome, approximately ten million protein-protein and protein-DNA interactions with an expected accuracy of 50%.
Utility in identifying function, essential proteins, and host pathogen interactions
Proteins PPIs TRIsH. sapiens 26,741 17,652 828,807 1,045,622S. cerevisiae 5,801 5,175 192,505 2,456O.sativa (6) 125,568 19,810 338,783 439,990E. coli 4,208 885 1,980 54,619
INFRASTRUCTURE
Guerquin/Frazier
http://bioverse.compbio.washington.eduhttp://protinfo.compbio.washington.edu
~500,000 molecules over 50+proteomes served using a 1.2 TB PostgreSQL database and a sophisticated AJAX webapplication and XML-RPC API
INFRASTRUCTURE
Chang/Rashid
http://bioverse.compbio.washington.edu/integrator
APPLICATION: DRUG DISCOVERY
HSV KHSVCMV
Computionally predicted broad spectrum human herpesvirus protease inhibitors is effective in vitroagainst members from all three classes and is comparable or better than anti-herpes drugs
HSVHSV
Our protease inhibitor acts synergistically with acylovir (a nucleoside analogue that inhibits replication) and it is less likely to lead to resistant strains compared to acylovir
Lagunoff
APPLICATION: NANOTECHNOLOGY
Oren/Sarikaya/Tamerler
FUTURE
Structuralgenomics
Functionalgenomics
+
Computationalbiology
+
MODELLING PROTEIN AND PROTEOME STRUCTURE FUNCTION AT THE ATOMIC LEVEL IS NECESSARY TO UNDERSTAND THE
RELATIONSHIPS BETWEEN SINGLE MOLECULES, SYSTEMS, PATHWAYS, CELLS, AND ORGANISMS
ACKNOWLEDGEMENTS
•Baishali Chanda •Brady Bernard•Chuck Mader •David Nickle •Ersin Emre Oren •Ekachai Jenwitheesuk •Gong Cheng •Imran Rashid•Jeremy Horst •Ling-Hong Hung •Michal Guerquin•Rob Brasier•Rosalia Tungaraza •Shing-Chung Ngan•Siriphan Manocheewa•Somsak Phattarasukol•Stewart Moughon •Tianyun Liu•Vania Wang•Weerayuth Kittichotirat •Zach Frazier•Kristina Montgomery, Program Manager
Current group members:•Aaron Chang•Duncan Milburn•Jason McDermott•Kai Wang•Marissa LaMadrid
Past group members:
Funding agencies:•National Institutes of Health•National Science Foundation•Searle Scholars Program•Puget Sound Partners in Global Health•UW Advanced Technology Initiative•Washington Research Foundation•UW TGIF
•James Staley•Mehmet Sarikaya/Candan Tamerler•Michael Lagunoff•Roger Bumgarner•Wesley Van Voorhis
Collaborators:
Recommended