Copyright Elsevier MDL 2007 Present and future of informatics in chemistry Symposium in Honor of Gary Wiggins Division of Chemical Information 223 rd ACS

Copyright Elsevier MDL 2007

Present and future of informatics in chemistrySymposium in Honor of Gary WigginsDivision of Chemical Information223rd ACS National Meeting, Chicago

Phil McHale Elsevier MDL25 March 2007

2 Copyright Elsevier MDL 2007

Outline

Informatics in chemistry?Where have we got to?What can we do now?What’s left to do?Where are we going?


Informatics in chemistry?

Cheminformatics vs. Chemoinformatics

Structure representation

Information acquisition

Information management

Information use


This Awful Neologism ….

Date: Fri, 17 Oct 1997 From: Wendy Warr

Subject: Re: Cheminformatics/Two new refs. I

wonder if any of the sources define this awful

neologism ("chemoinformatics" or

"cheminformatics"). Does it really differ from

"chemical information" or "computational

chemistry". As I have said before, I suspect

that it is merely an image-enhancing name

for some practitioners of computational

chemistry.


2 O or X 2 O?

Data copyrighted (C) by Molinspiration Cheminformatics. http://www.molinspiration.com/chemoinformatics.html

0

50000

100000

150000

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250000

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350000

400000

Jul-0

0

May

-01

Oct-01

Jun-

02

Jul-0

2

Aug-0

2

Sep-0

2

Oct-02

Jan-

03

Apr-0

3

Jun-

03

Aug-0

3

Nov-03

Feb-0

4

May

-04

Jul-0

4

Sep-0

4

Nov-04

Jan-

05

Mar

-05

Jul-0

5

Oct-05

Dec-05

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6

Sep-0

6

Dec-06

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-07

Date

Cit

atio

ns

0

0.5

1

1.5

2

2.5

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Rat

io

Cheminformatics

Chemoinformatics

Ratio


The Building Blocks

Molecules – 2D, 3D, stereoisomers,

conformers, polymers, mixtures,

formulations, sequences, combichem

libraries, virtual libraries, Markush….

Reactions – reagents, products, catalysts,

solvents, reacting centers, transition states,

metabolic pathways ….

Nomenclature, fragment codes, line

notations, graphics, file formats


Representing Chemistry: Benzene?

Connection table:Benzene -ISIS- 08200115272D

6 6 0 0 0 0 0 0 0 0999 V2000 -1.0306 -1.4375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0

0 -1.0318 -2.2648 0.0000 C 0 0 0 0 0 0 0 0 0 0 0

0 -0.3169 -2.6777 0.0000 C 0 0 0 0 0 0 0 0 0 0 0

0 0.3995 -2.2644 0.0000 C 0 0 0 0 0 0 0 0 0 0 0

0 0.3966 -1.4338 0.0000 C 0 0 0 0 0 0 0 0 0 0 0

0 -0.3187 -1.0247 0.0000 C 0 0 0 0 0 0 0 0 0 0 0

0 1 2 2 0 0 0 0 3 4 2 0 0 0 0 4 5 1 0 0 0 0 2 3 1 0 0 0 0 5 6 2 0 0 0 0 6 1 1 0 0 0 0M END

H

H

H

H

H

H H

H

H

H

H

H

b2u

a2u

e2u

e1g

Benzene

ID #: MUSE00000002

CAS #: 71-43-2

Other Names:BenzolCyclohexa-1,3,5-triene

Line notation•Wiswesser: RH

•MDL LN: C-C=C-C=C-C=@1

•SMILES: c1ccccc1

•InChI InChI=1/C6H6/c1-2-4-6-5-3-1/h1-6H


A Previous UI


But have we really progressed?

Subject: Re: Beilstein R-groups

From: Dana Roth <[log in to unmask]>

Reply-To: CHEMICAL INFORMATION SOURCES DISCUSSION LIST <[log in to unmask]>

Date: Fri, 16 Mar 2007 10:57:59 -0700

Content-Type: text/plainHoward: we are still teaching v.6 since most people here are using MACs. From my little experience with v.7, it appears that the structure editor is the same. I just followed these instructions (which I borrowed many years ago from Andrea Twiss-Brooks) in v.7 and it works fine.

=================

Creating User Defined Groups and Atom Lists Atoms: Click on the atom in the structure, which needs to be variable. Type 'A1' in the Atom Box and click OK to make the change. Next, click the 'An' button in the Tool Box (left side), and the 'Atom List Number' box will appear. Click OK to display a 'Define Atom List A1' periodic table. Click as many elements or element groups as needed and click OK. A list of the all the selected atoms will appear in the Structure Editor window. Groups: Click the atom, which will be the variable group in the structure. Type 'G1' in the Atom Box and click OK to effect the change. Next, draw a group in the Structure Editor window, 'Select' a group structure (i.e. by double clicking an atom or bond with the select tool) and click the 'Gn' button in the tool box. Set G=1 and click OK. Repeat for additional groups. One atom in each group must be designated as the attachment point. Click on this atom (with the Edit tool), to display the 'Atom Attributes box. Click 'Set User Defined' and then click 'Attachments'. Click '1' in the 'Attachment Points' box and click OK (in that box). Then click OK in the 'Atom Attributes' box. After drawing the structure, click on the Crossed Red Arrows à Beilstein Commander.


Information Acquisition:Structure tools and presentation

Structure drawing

Name structure converters

Virtual chemistry – de novo structure generation, enumeration

Chemical OCR: dead structure live structure

Text mining: text structure

Renderers - on screen, in print, within applications, 2D, 3D, shapes, animations


Data Management

Structure storage systems – online, in-house, local, distributed, open, closed, proprietary systems, Oracle cartridges

Registration, novelty check, definitions, business rules

Search systems

• Molecules, reactions

• 2D, 3D, conformations

• Exact, substructure, similarity, fuzzy, shape, property-based, pharmacophores

Pre/Post-search processing – fingerprints, clustering, filtering, diversity analysis

Performance and scalability – virtual chemistry


Information Use:What we can do now

“Publish” information in lab notebooks, databases, reports, papers, patents

Detect, analyze and harvest structures and reactions from printed materials

Create, maintain, publish and link to databases

Search, browse and analyze structures and reactions in databases and documents

Link structures with their properties and with other disciplines – pathways, proteins, genes

Virtual chemistry and sceening

Predict/calculate properties, activity, reactivity, drug-likeness

Render, share and communicate

Collaborate and reuse


Sample workflows

Finding out what’s known about a

molecule

Exploring possible synthetic routes

to a target molecule

Assessing metabolic and toxic liabilities

and outcomes


Search MDL Compound Index


Links to all indexed content










Exploring Possible Syntheses


Evaluating Metabolic and Toxic Liabilities

From one parent in MDL Metabolite

From one parent in MDL Metabolite

From another parent in MDL Metabolite

From another parent in MDL Metabolite

From Corporate Database

From Corporate Database

Link to Toxicity

Link to Toxicity

Transformation Details

Transformation Details


Evaluating Toxicity Information

Link to Toxicity


What’s left to do?

Structure Representation• Generic structures and patents

• More stereochemistry

• Organometallics, composites, stuff

• Biomolecules

• Transition states, reaction mechanisms, pathways

Information Acquisition• Authoring tools

• Annotation - semantics

• Web 2.0 – social networking, wikis


What else is left to do?

Information Management• Integration

• Performance

• Timeliness

• Accessibility

• Portability

Information Use• Better predictors: activity, ADMET, reactivity

• Better virtual screening

• Presenting QSAR results that chemists can act on

• Capturing and automating intellectual processes: synthesis design

• Knowledge extraction, inference generation


Where are we going?

Automated data capture and indexing

• Papers, patents, theses ….

Robust predictors and inference generators

Blurring of boundaries

• Internal and external information

• Text and structures

• Publications and databases

• Small molecules and -omics

• Mash ups

in cranio >> in silico >> in vitro


Thanks Gary

Documents

Copyright Elsevier MDL 2007 Present and future of informatics in chemistry Symposium in Honor of Gary Wiggins Division of Chemical Information 223 rd ACS