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.,

Cheminformatics Workflows Using Mobile

Apps for Drug Discovery

• mobile is revolutionary: a clean break

entirely new user interface

no backward compatibility

highly constrained resources

applicable to entirely new situations

mainframes

minicomputers

personal computers

portable laptops

mobile tablets

smartphones

?

The Computing Revolution #3

Williams et al DDT

16:928-939, 2011

Arnold and Ekins, PharmacoEconomics 28: 1-5, 2010

Williams et al., In collaborative computational technologies for

biomedical research 2011

Fitting Mobile Apps into R&D Workflow

Chemistry Apps • Reference data

• Education

• Structure drawing

• Database searching

• 3D viewing

• Reactions & collections

• Property calculation

• Model building

• Graphical presentation

• Data sharing

http://goo.gl/Goa4e

Need for dedicated website / store for science Apps

– find out more at www.scimobileapps.com

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

http://bit.ly/GzQ5ty

Green Solvents and Lab Solvents FREE Apps

Alex Clark made the App in 3 days

Android version – Lab Solvents

Includes GSK solvent data

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

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 idea of target Use of computational methods with TB is rare

30 years with little TB mouse in vivo data MIND THE TB GAP

IN V

IVO

INA

CT

IVE

IN V

IVO

AC

TIV

E

Pathway analysis

Binding site similarity to Mtb proteins

Docking

Bayesian Models - ligand similarity

Predicting the target/s for small molecules

TB molecules and target information database connects

molecule, gene, pathway and literature for >700 molecules

iPhone Android

TB Mobile layout on iPhone and 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

http://goo.gl/UTTH0

TB Mobile – poster on Jan 2013

http://goo.gl/vPOKS http://goo.gl/iDJFR

TB Mobile – Is on iTunes and Google play

and it is FREE

http://goo.gl/7fGFW

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

Connecting

data/tools

like a TB Spider

In vitro data

In vivo data

Target data

ADME/Tox data

& models

Drug-like scaffold creation

TB prediction tools TB publications

• 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...

TB Mobile in a TB Workflow

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...

http://molmatinf.com/

venice.html

To see the rest

of the TB

workflow……

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

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

27

Malabika Sarker, Carolyn Talcott, Joel Freundlich, Barry Bunin

2R42AI088893-02 “from the National Institute of Allergy And

Infectious Diseases. (PI: S. Ekins)

You can find me @. CDD Booth 653..

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

Acknowledgments