Transcript Quarterly Project Review Template

Present and future of
informatics in chemistry
Symposium in Honor of Gary Wiggins
Division of Chemical Information
223rd ACS National Meeting, Chicago
Phil McHale
Elsevier MDL
25 March 2007
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?
2
Copyright Elsevier MDL 2007
Informatics in chemistry?
Cheminformatics vs. Chemoinformatics
Structure representation
Information acquisition
Information management
Information use
3
Copyright Elsevier MDL 2007
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.
4
Copyright Elsevier MDL 2007
400000
4
350000
3.5
300000
3
250000
2.5
200000
2
Ratio
Citations
2 O or X 2 O?
Chemoinformatics
Ratio
150000
1.5
100000
1
50000
0.5
0
J
M ula 0
O y-00
c
Ju t- 0 1
n 1
J -0
Auul- 2
0
Seg- 02
O p- 02
c
Ja t- 0 2
Apn-02
J r- 0 3
Auun- 3
0
Nog- 0 3
F v- 3
Meb- 0 3
ay 04
Ju -04
S e l0
Nop- 04
Ja v-04
M n-0 4
a 5
Jur- 0
O l-05
Dect- 0 5
A c-05
Sepr- 5
0
Dep- 06
M c-0 6
ar 6
-0
7
0
Data copyrighted (C) by Molinspiration Cheminformatics. http://www.molinspiration.com/chemoinformatics.html
Date
5
Cheminformatics
Copyright Elsevier MDL 2007
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
6
Copyright Elsevier MDL 2007
Representing Chemistry: Benzene?
Benzene
Connection table:
b2u
Benzene
-ISIS- 08200115272D
ID #:
MUSE00000002
CAS #:
71-43-2
Other Names:
Benzol
Cyclohexa-1,3,5-triene
7
Copyright Elsevier MDL 2007
6 6 0 0
-1.0306
0
-1.0318
0
-0.3169
0
0.3995
0
0.3966
0
-0.3187
0
1 2 2 0
3 4 2 0
4 5 1 0
2 3 1 0
5 6 2 0
6 1 1 0
M END
e2u
0 0 0 0 0 0999 V2000
-1.4375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0
-2.2648
0.0000 C 0 0 0 0 0 0 0 0 0 0 0
-2.6777
0.0000 C 0 0 0 0 0 0 0 0 0 0 0
-2.2644
0.0000 C 0 0 0 0 0 0 0 0 0 0 0
-1.4338
0.0000 C 0 0 0 0 0 0 0 0 0 0 0
-1.0247
0.0000 C 0 0 0 0 0 0 0 0 0 0 0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
e1g
a2u
H
H
H
H
H
H
H
H
H
H
H
Line notation
•Wiswesser:
•MDL LN:
•SMILES:
•InChI
RH
C-C=C-C=C-C=@1
c1ccccc1
InChI=1/C6H6/c1-2-4-6-5-3-1/h1-6H
H
A Previous UI
8
Copyright Elsevier MDL 2007
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/plain
Howard: 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.
9
Copyright Elsevier MDL 2007
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
10
Copyright Elsevier MDL 2007
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
11
Copyright Elsevier MDL 2007
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
12
Copyright Elsevier MDL 2007
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
13
Copyright Elsevier MDL 2007
Search MDL Compound Index
14
Copyright Elsevier MDL 2007
Links to all indexed content
15
Copyright Elsevier MDL 2007
Links to all indexed content
16
Copyright Elsevier MDL 2007
Links to all indexed content
17
Copyright Elsevier MDL 2007
Links to all indexed content
18
Copyright Elsevier MDL 2007
Links to all indexed content
19
Copyright Elsevier MDL 2007
Exploring Possible Syntheses
20
Copyright Elsevier MDL 2007
Evaluating Metabolic and Toxic
Liabilities
Link to
Toxicity
From Corporate
Database
From another parent
in MDL Metabolite
21
Copyright Elsevier MDL 2007
From one parent in
MDL Metabolite
Transformation
Details
Evaluating Toxicity Information
Link to
Toxicity
22
Copyright Elsevier MDL 2007
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
23
Copyright Elsevier MDL 2007
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
24
Copyright Elsevier MDL 2007
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
25
Copyright Elsevier MDL 2007
Thanks Gary
26
Copyright Elsevier MDL 2007