Cheminformatics Workflows Using Mobile
Apps for Drug Discovery
Alex M. Clark1, Antony J. Williams2 and Sean Ekins3,4
1

Mo...
The Computing Revolution #3

?
personal computers
portable laptops
mainframes
minicomputers

•

mobile tablets
smartphones...
Fitting Mobile Apps into R&D Workflow

Williams et al DDT
16:928-939, 2011

Williams et al., In collaborative computationa...
Chemistry Apps
• Reference data
• Education
• Structure drawing
• Database searching
• 3D viewing

• Reactions & collectio...
Need for dedicated website / store for science Apps
– find out more at www.scimobileapps.com

http://goo.gl/Goa4e
Simple App Workflows
•

Look up structure in ChemSpider

•

Saving structure as molfile - open in MMDS

•

Run substructur...
A Bigger Vision
• Mobile chemistry originally intended to support
desktop workflows
• Mobile+Cloud can be a total replacem...
APPIFYING DATA - From PDF to Mobile App

http://bit.ly/GzQ5ty

Lots of data
but how to
make it useful
for chemists?
Chemis...
Green Solvents and Lab Solvents FREE Apps
Alex Clark made the App in 3 days

ACS Sustain Chem Eng 1: 8-13 (2013)

Android ...



TB Kills 1.6-1.7m/yr (~1 every 8 seconds)
1/3rd of worlds population infected!!!!



Multi drug resistance in 4.3% o...
IN VIVO INACTIVE IN VIVO ACTIVE

30MIND THE TB GAP in vivo data
years with little TB mouse
Predicting the target/s for small molecules

Pathway analysis
Binding site similarity to Mtb proteins
Docking
Bayesian Mod...
TB molecules and target information database connects
molecule, gene, pathway and literature for >700 molecules
TB Mobile layout on iPhone and Android

iPhone

Android
TB Mobile Molecule Detail and Links

iPhone

Android
Molecules active against Mtb evaluated in TB Mobile app
Workflow from sketching molecules in MMDS mobile app
to exporting and opening with TB Mobile
TB Mobile – poster on

Jan 2013

http://goo.gl/UTTH0
TB Mobile – Is on iTunes and Google play
and it is FREE

http://goo.gl/vPOKS

http://goo.gl/iDJFR

http://goo.gl/7fGFW
What next ?







Update with more data
Add a weighting or scoring function to account
for heavily populated targets...
In vitro data
In vivo data

Target data

ADME/Tox data
& models
Connecting
data/tools
like a TB Spider
Drug-like scaffold ...
TB Mobile in a TB Workflow
•

Preliminary work done with desktop software: com.mmi

•

Fragment TB Mobile structures, scaf...
Source Materials
•

Scaffold:

•

Scaffold origin: inhibitor of Glf target

•

87 molecules with in vitro activity (yes/no...
Open Drug Discovery Teams

•
•

Curation of open data, e.g. Twitter & RSS feeds
Rare & neglected diseases, precompetitive
...
Harvested Tweet

•
•

Tweet got harvested into Tuberculosis topic
Inline preview browsed, with other
thumbnails
What we can do now…
Take HTS screening hits
Query public databases
Propose targets

Design / purchase analogs
Predict acti...
27

Conclusion
•

Cheminformatics workflows historically the role of
specialists: expensive and/or complex

•

Mobile apps...
Acknowledgments




Malabika Sarker, Carolyn Talcott, Joel Freundlich, Barry Bunin
2R42AI088893-02 “from the National In...
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Cheminformatics Workflows Using Mobile Apps for Drug Discovery

  1. 1. Cheminformatics Workflows Using Mobile Apps for Drug Discovery Alex M. Clark1, Antony J. Williams2 and Sean Ekins3,4 1 Molecular Materials Informatics, 2 Royal Society of Chemistry, 3Collaborations in Chemistry, 4 Collaborative Drug Discovery, Inc.,
  2. 2. The Computing Revolution #3 ? personal computers portable laptops mainframes minicomputers • mobile tablets smartphones mobile is revolutionary: a clean break  entirely new user interface  no backward compatibility  highly constrained resources  applicable to entirely new situations
  3. 3. Fitting Mobile Apps into R&D Workflow Williams et al DDT 16:928-939, 2011 Williams et al., In collaborative computational technologies for biomedical research 2011 Arnold and Ekins, PharmacoEconomics 28: 1-5, 2010
  4. 4. Chemistry Apps • Reference data • Education • Structure drawing • Database searching • 3D viewing • Reactions & collections • Property calculation • Model building • Graphical presentation • Data sharing
  5. 5. Need for dedicated website / store for science Apps – find out more at www.scimobileapps.com http://goo.gl/Goa4e
  6. 6. Simple App Workflows • Look up structure in ChemSpider • Saving structure as molfile - open in MMDS • Run substructure search in ChEBI using MMDS webservice • Open molecule from MMDS and assign scaffolds in SAR Table Generate substituents • Predict missing activities for compounds in SAR Table • Suggest compounds to make in SAR Table • Find a reaction in SPRESImobile • Use Yield101 to calculate synthesis yield • Share data with Dropbox using MolSync app • Tweet a reaction with MolSync • Read the data with ODDT mobile app Clark AM, Williams AJ and Ekins S, Chem-Bio Informatics Journal, 13: 1-18 2013.
  7. 7. A Bigger Vision • Mobile chemistry originally intended to support desktop workflows • Mobile+Cloud can be a total replacement • Entirely new user expectations for apps: - easy to learn - delightful to use - trivial to install - inexpensive or FREE • Extremely disruptive to existing software vendors!
  8. 8. APPIFYING DATA - From PDF to Mobile App http://bit.ly/GzQ5ty Lots of data but how to make it useful for chemists? Chemists see structures PDF not accessible, small text- too much data
  9. 9. Green Solvents and Lab Solvents FREE Apps Alex Clark made the App in 3 days ACS Sustain Chem Eng 1: 8-13 (2013) Android version – Lab Solvents Includes GSK solvent data
  10. 10.   TB Kills 1.6-1.7m/yr (~1 every 8 seconds) 1/3rd of worlds population infected!!!!  Multi drug resistance in 4.3% of cases Extensively drug resistant increasing incidence No new drugs in over 40 yrs until Bedaquiline Drug-drug interactions and Co-morbidity with HIV  Increase in HTS phenotypic screening  1000’s of hits no  Use of computational methods with TB is rare    idea of target
  11. 11. IN VIVO INACTIVE IN VIVO ACTIVE 30MIND THE TB GAP in vivo data years with little TB mouse
  12. 12. Predicting the target/s for small molecules Pathway analysis Binding site similarity to Mtb proteins Docking Bayesian Models - ligand similarity
  13. 13. TB molecules and target information database connects molecule, gene, pathway and literature for >700 molecules
  14. 14. TB Mobile layout on iPhone and Android iPhone Android
  15. 15. TB Mobile Molecule Detail and Links iPhone Android
  16. 16. Molecules active against Mtb evaluated in TB Mobile app
  17. 17. Workflow from sketching molecules in MMDS mobile app to exporting and opening with TB Mobile
  18. 18. TB Mobile – poster on Jan 2013 http://goo.gl/UTTH0
  19. 19. TB Mobile – Is on iTunes and Google play and it is FREE http://goo.gl/vPOKS http://goo.gl/iDJFR http://goo.gl/7fGFW
  20. 20. What next ?      Update with more data Add a weighting or scoring function to account for heavily populated targets Expand beyond the similarity measure Add algorithms to predict activity Could we appify data for other diseases/ targets
  21. 21. In vitro data In vivo data Target data ADME/Tox data & models Connecting data/tools like a TB Spider Drug-like scaffold creation TB prediction tools TB publications
  22. 22. TB Mobile in a TB Workflow • Preliminary work done with desktop software: com.mmi • Fragment TB Mobile structures, scaffold-like • Perform scaffold-substructure vs. 7000 in vitro • Derive R-groups, tidy, present graphically, browse...
  23. 23. Source Materials • Scaffold: • Scaffold origin: inhibitor of Glf target • 87 molecules with in vitro activity (yes/no) • Scaffold seems to elicit an activity pattern • Next step: load it into the app ecosystem... To see the rest of the TB workflow…… http://molmatinf.com/ venice.html
  24. 24. Open Drug Discovery Teams • • Curation of open data, e.g. Twitter & RSS feeds Rare & neglected diseases, precompetitive areas
  25. 25. Harvested Tweet • • Tweet got harvested into Tuberculosis topic Inline preview browsed, with other thumbnails
  26. 26. What we can do now… Take HTS screening hits Query public databases Propose targets Design / purchase analogs Predict activity All on a mobile device / anywhere
  27. 27. 27 Conclusion • Cheminformatics workflows historically the role of specialists: expensive and/or complex • Mobile apps are much cheaper and much more accessible to experimentalists • Mobile+cloud can: - replace simple-to-medium tasks - coexist with complex tasks run on desktop software • Other advantages: - anywhere/anytime portability - excellent collaboration and sharing - non-existent installation or maintenance burden
  28. 28. Acknowledgments   Malabika Sarker, Carolyn Talcott, Joel Freundlich, Barry Bunin 2R42AI088893-02 “from the National Institute of Allergy And Infectious Diseases. (PI: S. Ekins) Poster 224 PAPER TITLE: “Dual Response and dataset Fusion for Machine Learning Models for Hit to lead Optimization in Mycobacterium Tuberculosis Drug Discovery” Monday, January 20, 2014 Presentation Time: 1:00 PM – 3:00 PM You can find me @. CDD Booth 653..

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