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INTERACTOMICS RAM SAMUDRALA ASSOCIATE PROFESSOR UNIVERSITY OF WASHINGTON

INTERACTOMICS RAM SAMUDRALA ASSOCIATE PROFESSOR UNIVERSITY OF WASHINGTON NIH DIRECTOR’S PIONEER AWARD 2010 How does the genome of an organism specify its behaviour and characteristics? How can we use this information to improve human health and quality of life?

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INTERACTOMICS RAM SAMUDRALA ASSOCIATE PROFESSOR UNIVERSITY OF WASHINGTON

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  1. INTERACTOMICS RAM SAMUDRALA ASSOCIATE PROFESSOR UNIVERSITY OF WASHINGTON NIH DIRECTOR’S PIONEER AWARD 2010 How does the genome of an organism specify its behaviour and characteristics? How can we use this information to improve human health and quality of life? COMPUTATIONAL ANALYSIS OF NOVEL DRUG OPPORTUNITIES THE CANDO TEAM cando.compbio.washington.edu

  2. GENOME SEQUENCE TO PROTEIN AND PROTEOME… FUNCTION INTERACTION STRUCTURE DNA/RNA PROTEIN COMPOUND SYSTEMS INFRASTRUCTURE APPLICATIONS RICE THERAPEUTICS DESIGN NANOTECHNOLOGY EVOLUTION

  3. SHOTGUN DRUG REPURPOSING ALL KNOWN DRUGS (~5,000 FROM FDA) FRAGMENT BASED DOCKING WITH DYNAMICS (~120,000,000) PRIORITISED HITS DISSOCIATION CONSTANTS (KD) (~300-500 + collaborations) + ALL TARGETS WITH KNOWN STRUCTURE (~80,000+) MACHINE LEARNING IN VITRO STUDIES INITIAL CLINICAL TRIALS IN VIVO STUDIES herpes, malaria, dengue hepatitis C, dental caries HIV, HBRV, XMRV, rabies, encephalitis, cholera, tuberculosis, various cancers, and many more: cando.compbio.washington.edu CLINICAL STUDIES/APPLICATION M Lagunoff (UW), W Van Voorhis (UW), S Michael (FCGU), J Mullins (UW), G Wong/A Mason/L Tyrell (U Alberta), W Chantratita/P Palittapongarnpim (Thailand) Many more at cando.compbio.washington.edu

  4. PROSPECTIVE PRELIMINARY VERIFICATION HERPES (HSV, CMV, KSHV) DENGUE Predicted protease (dimer) + inhibitor: Viral E protein Prediction #1 Prediction #2 Observed: Function is inactivated. KD protease ligand ≤μM KD protease dimer ≤ μM Experiment 1 Experiment 2 2/4 ≤µM ED50 against dengue virus Herpes viral load PLoS Neglected Tropical Diseases, 2010. MALARIA 14 targets Multitarget protocol: 2,344 → 16 → 6 ≤ 1 µM ED50 HTS protocol: 2,687 → 19 ≤ 1 µM ED50 HTS protocol: 2,160 → 36 ≤ 1 µM ED50 Docking protocol: 355,000 → 100 → 1 ≤ 10 µM ED50 Docking protocol: 241,000 → 84 → 4 ≤ 10 µM ED50 Trends in Pharmacological Sciences, 2010. Lagunoff/ Van Voorhis/ Michael

  5. NEISSERIA MENINGITIDIS Schneider et al. Nature, 2009. Topamax Voacamine Treatement of epilepsy Anti malarial agent Loop movement breaks the interface factor H binding protein from Neisseria meningitidis mimics host carbohydrates and recruits host factor H to protect against the complement immune response Homo sapiens factor H Neisseria meningitidis factor H binding protein Chopra/White

  6. ACKNOWLEDGEMENTS Current group members: Past group members: • Adrian Laurenzi • Brian Buttrick • Emilia Gan • Ersin Emre Oren • Gaurav Chopra • George White • Haychoi Taing • Helen Yu • Hernan Zamalloa • Jason North • Jeremy Horst • Ling-Hong Hung • Matthew Clark • Manish Manish • Michael Zhou • Nalini Schaduangat • Omid Zarei • Raymond Zhang • Sai Paul • Sergey Ovchinnikov • Thomas Wood • Aaron Chang • Aaron Goldman • Brady Bernard • Chuck Mader • Cyrus Hui • David Nickle • Duangdao Wichadukul • Duncan Milburn • Ekachai Jenwitheesuk • Gong Cheng • Imran Rashid • Jason McDermott • Juni Lee • Kai Wang • Marissa LaMadrid • Michael Inouye • Michael Shannon • Michal Guerquin • Nipa Jongkon • Rob Braiser • Renee Ireton • Shu Feng • Sarunya Suebtragoon • Shing-Chung Ngan • Shyamala Iyer • Siriphan Manocheewa • Somsak Phattarasukol • Stewart Moughon • Tianyun Liu • Vanessa Steinhilb • Vania Wang • Weerayuth Kittichotirat • Yi-Ling Cheng • Zach Frazier CANDO TEAM MEMBERS IN BLUE: CURE OR TREAT DISEASES CURRENTLY UNTREATED

  7. ACKNOWLEDGEMENTS Collaborators: • BGI/U Alberta • Gane Wong • Jun Yu • Jun Wang • Andrew Mason • Lorne Tyrell • BIOTEC/KMUTT • Mahidol University • - Prasit Palittapongarrnpim • - Wasun Chantratita • MSE • Mehmet Sarikaya • Candan Tamerler • et al. • UW Microbiology • James Staley • John Mittler • Michael Lagunoff • Roger Bumgarner • Wesley Van Voorhis • et al. Funding agencies: • National Institutes of Health • National Science Foundation • -DBI • -IIS • Searle Scholars Program • Puget Sound Partners in Global Health • Washington Research Foundation • UW • -Advanced Technology Initiative • -TGIF • Budget: • ~US$1 million/year total costs

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