This document summarizes the development of a chemical library design tool at Dart NeuroScience. It describes the goals of creating an easy to use tool to standardize calculations, reactions, and simplify workflows. The tool was developed using KNIME with ChemAxon services and utilizes a service oriented architecture. Key features of the tool include reactant selection, reaction enumeration, property calculations, clustering, and exporting designs to Spotfire and ELNs. The tool has been iteratively improved over several years of development and testing.

1. A ChemAxon/KNIME based tool
for designing chemical libraries
Tim Parrott
Dart NeuroScience
September 25, 2013
Brock Luty
Dart NeuroScience
ChemAxon UGM

2. Dart NeuroScience
Small molecules to maintain
cognitive vitality (LTM)
Currently about 200 FTEs with
build-out expected at 260
Privately held LLC by a single
individual

3. Scientific Computing
Scientific Computing collaborates with other DNS
Departments to deliver solutions that simplify and
accelerate the drug discovery process.
We rely on our (non-traditional) knowledge and
experience in both Science and Technology to develop
novel and efficient systems to meet this goal

4. Scientific Computing Groups
Bioinformatics
Philip Cheung
Doug Fenger
+ 1 FTE
Information
Management
+ 1 Group Lead
John Jaeger
Tim Parrott
James Harr
Eileen Tompkins
Heather Jones
Methods
Development
Ron Blanford
Daniel Garden
Kevin Neal
Hari Muddana
+ 1 FTE
Computational
Chemistry
*Tami Marrone
Meg McCarrick
James Na
Amy Shih
Bill Sinko
Project Support
- Modeling
- SBDD/Library Design
- Apply Methods
- Pre-LO/LO/PCC
Data / Biz Analysis
- Data Capture
- Analytics
- Data Access
- QA/Scientific Support
- Project Management
Software Development
- Informatics Software Development
- Developing new methods
- Enterprise Scale Architecture
- RIA (MVC) with SOA
- Extensions for ELN, Spotfire, IJC, etc
Project Support
- Target ID
- Expression Analysis / Pathways
- Novel Software algorithms
- Enterprise Software (with Methods)

5. Background
Dart NeuroScience (DNS)
200+ Scientists
50+ Chemists
Parallel Synthesis Group
About 20 chemists involved in
the design and creation of
chemical libraries
We need a
chemical library
design tool !

6. A Basic Chemical Library Design Tool
Enumerate Products
Calculate Properties
Analyze & Filter
Select Reactants
DesignTest
Analyze
Synthesize

7. Goals
SupportEase of Use
Productivity
Standardize calculations &
reactions (services)
Simplify: wrap processes and
minimize import/export operations
Enhance capabilities and speed by
doing calculations remotely
Constraints
Limited IT/IM support
Chemists already on
software overload
Approach
=

8. Chemical Property
Calculations,
Reaction
Enumeration
Data Pipelining
Visualization /
Analytics
3D Scoring
Platforms

9. Architecture
Heavily invested in Service Oriented architecture (Rest Style API) with
standardized DNS patterns
Domain CRUD (Create, Read, Update, Delete) GUIs written for specific
entities using MVC pattern (relying on Backbone.js and standardized
DNS patterns)
Traditional Stateless Computational Services (Property Calculation,
Enumeration, etc)
Services can be based on Scripts using command-line applications (primary
use-case). Services can also be written on KNIME and run in this
architecture.
Move all the heavy lifting to the servers (automated parallelization). KNIME
as a Service Orchestration Layer
Application
Service
Database
Brock’s Geeky
Slide

10. Tool Overview
Selection &
Configuration
Panel
Custom
Nodes
Spotfire
Export

11. Reactant Selection
Import curated
classes of
reactants
(CRUD Service)

12. Reactant Selection
Import list of
Reagent Numbers
(CRUD Service)

13. Reactant Deduplication
Input Output
Need to identify and
remove functionally
equivalent reactants
(Comp Service)

14. Reaction Selection

15. Reactions: A Look under the Hood
“Reactor” nodes
can contain multi-
step workflows.
(Comp Services)
Server-Side

16. Calculations

17. Clustering
Server-Side

18. Calculations --- OpenEye ROCS
ROCS output includes the
Shape/Pose that scored
best and the Tanimoto
Score against that query.
(Computational Service)

19. Pausing Local Execution

20. Export to Spotfire

21. Selections made in Spotfire

22. Spotfire Selections returned to KNIME
New nodes with
selected products
& reactants
appear in KNIME

23. Final Steps
The library design plan contains
separate sdf files for the products
and each reactant, along with a .csv
file listing how many times each
reactant is used. The zipped file is
parsed on import into a chemist’s
electronic laboratory notebook.
Stereochemical codes
needed for registration
are assigned based on
structure.
(Computational Service)

24. Load Library Design Plan into the
Agilent ELN
Custom Forms for
planning and
products tables

25. Summary
• June 2011
• June 2012
• Sept 2012
• November 2012
• April 2013
• August 2013
Parallel Synthesis Group formed
First release of Library Design Tool (LDT)
Additional KNIME training
Second release (Clustering, ROCS)
Pausable Nodes, Deduplication
RN Lookup, Stereo Code Assigner
40 Total Reactions

26. Acknowledgments
Node Development
Services & Deployment Testing and troubleshooting
Management & PM
loki der quaeler
Ron Blanford
Karen Do
Kenny Leung
Zach Young
Daniel Garden
Eileen Tompkins
Andrew Burritt
The SGC Team
Melanie Nelson
Heather Jones
Brock Luty