A chemical workbench for Biopolymers

ChemAxon User Group Meeting

April, 2017

Joshua A. Bishop, Ph.D.CPH IT & Informatics - MRL IT

2

Compound Design & Synthesis Information Cycle

Biological

Testing

Purification

& Registration

Chemical

Synthesis

Design

& Selection

Hypothesis

Generation

Analysis &

Decision-making

Perceived gaps

Capture of valuable high-throughput chemistry

data and use of ELN reactions

Tracking of designs & work-in-progress

Cheminformatics tools integration w/

Spotfire

Building block search and

selection

Data Access

Approach

Adopt services-oriented

architecture from the ground up

Reusable web-components where

possible

Leverage a Data Platform for

ingestion and aggregation

Biopolymer Workbench - Objectives

3

Goal 1 – Fill unmet gaps in workflow for biopolymer chemists

Goal 1a – Fill unmet TECHNOLOGY gaps as to fill unmet gaps in workflow…

Property

CalculationsAutomated

SynthesisRegistration Purification SAR Tools

COTS

Solutionjavascript

Perception

Engine

Biopolymer Design-Make-Test

Scientific Workflow

4

Biopolymer

Calculator 1

Biopolymer

Calculator 2

Biopolymer

Calculator 3

Export .txt file suitable for

synthesis robotics

Enumerate

desired library

Synthesize

desired library

Screen libraries across

biological assaysPush to

requested assays

Register and purify

successful syntheses

Assay result analysis

Biopolymer SAR tools

HELM

Monomer

Library

Biopolymer Design enumerator

= BioEddie use/services/integration

Biopolymer Design-Make-Test

Technology Stack

5

BP enumerator

HELM monomer

library

BP property calculator 1

Registered virtual

and real biopolymers

BP synthesis request

and registration

Assay Data

BP SAR

Tools

SIM Data Platform

Assay Data collection

BP property calculator 2 BP property calculator 3

Registered

small molecules Databases

Aggregation

Services

Applications

Biopolymer Enumeration and Design

6

Enumeration and DesignBP virtual

registration

MS directed

Synthesis verification

Assay Request

SAR Analysis

Purification and

Formal BP Registration

Robotic Synthesizers

MerMades

BP sequence:

CEXISYZLP

Variables:

X = C,L,P,E, [dMc]

Y = [aI],L,E,R

Z = S,[giT],R,I

EnumerateVirtual Library

Virtual Library

Biopolymer

Specific Calculations

and Predicted Properties Synthesis

Selection

Biopolymer Enumeration Tools

7

Launch BioEddie

Choose HELM file

Enter position(s) to be changed

Enter monomer codes to be changed

Biopolymer Design

Discngine, BioEddie and Spotfire

8

Biopolymer Synthesis Execution Tools

9

BP Virtual registration

BioReg

HELM

Monomer

Library

Robotic Synthesizers

MerMades

PLP

Design and

Enumeration

MS directed

Synthesis verificationMerMade

Monomer

Library

Assay Request

SAR Analysis

Purification and

Formal BP Registration

Registration

and perception

How user interacts in sketcher with entity

How data base interprets

and stores input

NO NEW templates

detected

Registration

and perception

How user interacts in sketcher with entity

NEW templates

detected

Your structure appears to have

novel monomers.

Please remediate.

Show monomers to user that are

not present in library, assign 3

letter code per business rules,

verify with user accuracy, push to

central monomer library

Complete registration

Complex Biopolymers & Singleton/Small Scale DMT

How data base interprets

and stores input

Biopolymer Purification

11

Design and

Enumeration

MS directed

Synthesis verification

Assay Request

SAR Analysis

Virtual

RegistrationSynthesis

Purification and

Formal BP Registration

HELM FileEKB purification

workflow

HELM

Monomer

Library

Assay Request

and SAR Analysis

Biopolymer SAR Tools

12

Design and

Enumeration

MS directed

Synthesis verification

Virtual

RegistrationSynthesis

Purification and

Formal BP Registration

Data Platform

IngestionSpotfire visuals and

BP SAR Tools

Biopolymer SAR Tools – mockups

13

Biopolymer SAR Tools – mockups

14

Biopolymer SAR Tools – mockups

15

Biopolymer SAR Tools – mockups

16

Biopolymer Design-Make-Test

Scientific Workflow

17

Biopolymer

Calculator 1

Biopolymer

Calculator 2

Biopolymer

Calculator 3

Export .txt file suitable for

synthesis robotics

Enumerate

desired library

Synthesize

desired library

Screen libraries across

biological assaysPush to

requested assays

Register and purify

successful syntheses

Assay result analysis

Biopolymer SAR tools

HELM

Monomer

Library

Biopolymer Design enumerator

= BioEddie use/services/integration

18

Acknowledgments

Farida Kopti

Matt Walker

Jay Mehta

Charlie Chang

Chris McNally

Iain Wallace

Angie Kantola

Chris Waller

Mark Schreiber

MRL

Rich Tillyer

Rob Garbaccio

Brad Sherborne

Sookhee Nicole Ha

David Tellers

Greg Adams

Songnian Li

Dmitri Pissarnitski

Craig Parish

Tony Siu

Claudio Mapelli

Sustaining Partners

ChemAxon

EPAM

Discngine

MRL IT