Cheminformatics Workflows Using Mobile Apps for Drug Discovery
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Cheminformatics Workflows Using Mobile Apps for Drug Discovery



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Cheminformatics Workflows Using Mobile Apps for Drug Discovery Cheminformatics Workflows Using Mobile Apps for Drug Discovery Presentation Transcript

  • 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.,
  • 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
  • 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 View slide
  • Chemistry Apps • Reference data • Education • Structure drawing • Database searching • 3D viewing • Reactions & collections • Property calculation • Model building • Graphical presentation • Data sharing View slide
  • Need for dedicated website / store for science Apps – find out more at
  • 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.
  • 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!
  • APPIFYING DATA - From PDF to Mobile App Lots of data but how to make it useful for chemists? Chemists see structures PDF not accessible, small text- too much data
  • 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
  •   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
  • 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 Models - ligand similarity
  • 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
  • TB Mobile – Is on iTunes and Google play and it is FREE
  • 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
  • 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
  • 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...
  • 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…… venice.html
  • Open Drug Discovery Teams • • Curation of open data, e.g. Twitter & RSS feeds Rare & neglected diseases, precompetitive areas
  • 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 activity All on a mobile device / anywhere
  • 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
  • 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..