Going a mile InChI by InChI Enabling online chemistry at ChemSpider Antony Williams

Languages of Chemistry

ChemSpider 2009 “ Building a Structure Centric Community for Chemists” Hosting structures, spectra, images, documents, outlinks Many web services for retrieval of data, conversion of files, generation of properties.. Now a platform for: data deposition, curation and annotation – remove the junk Supporting Open Notebook Science efforts chemistry document mark-up with ChemMantis the online ChemSpider Journal of Chemistry

“ Building a Structure Centric Community for Chemists”

Hosting structures, spectra, images, documents, outlinks

Many web services for retrieval of data, conversion of files, generation of properties..

Now a platform for:

data deposition, curation and annotation – remove the junk

Supporting Open Notebook Science efforts

chemistry document mark-up with ChemMantis

the online ChemSpider Journal of Chemistry

Statistics and Connections >6000 unique users per day on average >40,000 transactions per day >21.4 million compounds and growing daily Advocate of InChIs for searching and integration

>6000 unique users per day on average

>40,000 transactions per day

>21.4 million compounds and growing daily

Advocate of InChIs for searching and integration

Search Cholesterol

Search Cholesterol

Search Cholesterol

Search Cholesterol

Search Cholesterol

Search Cholesterol

Searching Structure searching based on SMILES InChIString InChIKey StdInChI StdInChIKey molfile uploads structures drawn in applet Search across Google (to string limit for InChIString) Skeleton search Full structure search

Structure searching based on

SMILES

InChIString

InChIKey

StdInChI

StdInChIKey

molfile uploads

structures drawn in applet

Search across Google (to string limit for InChIString)

Skeleton search

Full structure search

InChIKey Searches Work

Depositions Depositions from users – single structures and SDFs Depositions from databases/vendors – SDF files And then came InChIs… InChIs and InChIKeys are available on Blogs for harvesting Publishers are making their structures available as InChIs for harvesting InChIs are NOT ideal for building a database…some lessons We want to link to publications especially…

Depositions from users – single structures and SDFs

Depositions from databases/vendors – SDF files

And then came InChIs…

InChIs and InChIKeys are available on Blogs for harvesting

Publishers are making their structures available as InChIs for harvesting

InChIs are NOT ideal for building a database…some lessons

We want to link to publications especially…

Chemistry Papers Cultivation of a rare Verrucosispora strain (sediment, Sea of Japan) gave three polyketides, atrop -abyssomicin C 35 , abyssomicin G 36 and abyssomicin H 37 . Atrop -abyssomicin C 35 has previously been reported as a synthetic compound, but ready conversion to abyssomicin D suggests that it was probably naturally produced. Atrop -abyssomicin C was an inhibitor of S. aureus N315 (MRSA) and 4-amino-4-deoxychorismate (ADC) synthase. The tenacibactins A–D 38 – 41 , hydroxamate siderophores isolated from culture of the filamentous bacterium Tenacibaculum sp. ( Chondrus ocellatus , Awajishima Island, Japan), all possessed iron-chelating activity with tenacibactins C 40 and D 41 being considerably more effective than tenacibactins A 38 and B 39 .

Cultivation of a rare Verrucosispora strain (sediment, Sea of Japan) gave three polyketides, atrop -abyssomicin C 35 , abyssomicin G 36 and abyssomicin H 37 . Atrop -abyssomicin C 35 has previously been reported as a synthetic compound, but ready conversion to abyssomicin D suggests that it was probably naturally produced. Atrop -abyssomicin C was an inhibitor of S. aureus N315 (MRSA) and 4-amino-4-deoxychorismate (ADC) synthase. The tenacibactins A–D 38 – 41 , hydroxamate siderophores isolated from culture of the filamentous bacterium Tenacibaculum sp. ( Chondrus ocellatus , Awajishima Island, Japan), all possessed iron-chelating activity with tenacibactins C 40 and D 41 being considerably more effective than tenacibactins A 38 and B 39 .

Structures in Chemistry Papers

Aesthetics vs Machine Readable Beautiful chemical structures submitted by authors can be beasts for machines

Beautiful chemical structures submitted by authors can be beasts for machines

InChI Representation

InChI’fication of Articles InChIs from publishers – a lot of work for a publisher to provide exact structures for articles. Applause to RSC for Project Prospect and now Nature Chemistry An enormous editorial task with a massive benefit to the community If the structures were correct…imagine a centralized DOI:InChI database

InChIs from publishers – a lot of work for a publisher to provide exact structures for articles. Applause to RSC for Project Prospect and now Nature Chemistry

An enormous editorial task with a massive benefit to the community

If the structures were correct…imagine a centralized DOI:InChI database

Cleaning Structures

Converting InChIs to Structures Bacitracin A InChI=1/C66H103N17O16S/......./t35 u ,36 u ,37 u ,40-,41+,42+,43-,44+,45-,46-,47+,48 u ,52-,53-,54-/m0/s1 InChI=1/C66H103N17O16S/.......)/t35 ? ,36 ? ,37 ? ,40-,41+,42+,43-,44+,45-,46-,47+,48 ? ,52-,53-,54-/m0/s1

InChI=1/C66H103N17O16S/......./t35 u ,36 u ,37 u ,40-,41+,42+,43-,44+,45-,46-,47+,48 u ,52-,53-,54-/m0/s1

InChI=1/C66H103N17O16S/.......)/t35 ? ,36 ? ,37 ? ,40-,41+,42+,43-,44+,45-,46-,47+,48 ? ,52-,53-,54-/m0/s1

Converting InChIs to Structures What we want is a good layout, retention of stereochemistry labels and tautomers as drawn

What we want is a good layout, retention of stereochemistry labels and tautomers as drawn

Auxinfo – Who Uses It? Who Converts It? AuxInfo=1/1/N:52,24,90,40,41,50,100,60,51,23,61,68,66,67,17,16,83,65,64,15,81,30,28,84,92,37,62,99,74,71,13,45,11,39,49,22,59,63,9,88,79,31,35,95,98,75,70,42,76,25,5,47,19,56,77,86,78,26,34,93,7,6,53,18,55,44,85,2,48,12,91,10,80,33,14,38,96,73,69,94,43,58,21,1,27,32,3,4,89,87,82,29,36,97,8,72,54,20,57,46/E:(4,5)(13,14)(18,19)(85,86)(87,88)/it:im/rA:100cONOOCCCOCNCNCNCCCCCONCCCCCOCOCCONCCOCNCCCCNCCSCNCCCCCOCCONCCCCCCCCCCNCCONCCCCCCNCOCCNCOCOCNCCNCNOCCC/rB:;;;s3d4;;;d7;;s9;s10;d11;d9s12;;;;s15s16;s14;s18;d18;N19;s19;s22;s23;;s21;d25;s25;d26;s28;s26s30;s25;N31;s33;s34;d34;s35;N35;s37;s39;s39;;s42;d43;s42;s44s45;s44;s47;s47;s49;s49;s51;s38s42;d53;;s55;d55;P56;s56;s59;s59;;s62;d63;s63;d65;s64;s66d67;s7;s6p69;s5s70;d6;s6;;n73s74;d1s2s74;s75;s58;s78;N79;s79;d78;s81;s83;s84;s80;d86;p14s15s86;d77;s61;s77;s16s91;;s55;s62s93p94;s93;d93;s7n96;s9s98;s22;/rC:12.1656,-8.504,0;12.1656,-6.2884,0;16.5968,-3.1336,0;15.3445,-5.2769,0;16.5968,-4.5785,0;16.7654,-7.5166,0;20.0406,-7.5166,0;20.0406,-6.2402,0;22.208,-6.2161,0;23.2436,-5.4937,0;22.8582,-4.2895,0;21.6059,-4.2895,0;21.1725,-5.4937,0;19.294,-19.028,0;16.067,-19.6542,0;11.2264,-17.9202,0;13.1048,-19.6542,0;20.45,-18.426,0;21.5337,-19.028,0;20.45,-17.1255,0;21.5578,-21.1954,0;22.6174,-18.4019,0;22.6174,-17.1255,0;23.7252,-16.4512,0;19.2459,-23.9168,0;22.7137,-21.8698,0;19.2699,-25.2654,0;20.4018,-23.2425,0;23.8697,-21.1714,0;21.5819,-23.8927,0;22.7378,-23.1943,0;18.0899,-23.2665,0;23.9179,-23.8686,0;25.0497,-23.1702,0;26.2298,-23.8686,0;25.0497,-21.8457,0;27.3617,-23.1702,0;26.2298,-25.2172,0;27.3617,-21.8457,0;28.5417,-21.1714,0;26.2298,-21.1714,0;28.5417,-25.2172,0;29.8181,-25.6025,0;30.6128,-24.5188,0;28.5417,-23.8686,0;29.8181,-23.411,0;31.9614,-24.5188,0;32.6357,-25.6989,0;32.6357,-23.3629,0;31.9614,-22.2069,0;33.9603,-23.3629,0;34.6346,-24.5188,0;27.3617,-25.8675,0;27.3617,-27.2161,0;20.0165,-11.3457,0;18.9328,-11.9959,0;20.0165,-10.0452,0;18.9087,-13.3686,0;17.825,-11.3457,0;16.7172,-11.9959,0;17.825,-10.0693,0;23.5807,-11.7551,0;23.5807,-13.0315,0;24.7367,-13.6817,0;22.5211,-13.6817,0;22.5211,-14.9822,0;24.7367,-14.934,0;23.5807,-15.5842,0;18.9328,-8.1427,0;17.8009,-7.5166,0;17.8009,-5.2769,0;16.091,-6.3365,0;16.1633,-8.6003,0;14.0681,-7.3962,0;14.7906,-8.6003,0;12.8158,-7.3962,0;14.0681,-9.8044,0;17.5119,-13.3686,0;16.8135,-14.5728,0;17.5119,-15.7528,0;15.4408,-14.5728,0;17.0699,-12.6613,0;14.7665,-15.7528,0;13.3697,-15.7528,0;12.6713,-16.9569,0;16.8135,-16.9569,0;15.4408,-16.9569,0;17.5119,-18.137,0;14.7906,-10.9845,0;19.0291,-9.395,0;12.6954,-9.8044,0;11.2264,-11.1049,0;22.2321,-10.0452,0;21.1243,-11.9478,0;22.2321,-11.3457,0;21.1243,-9.4191,0;23.3399,-9.4191,0;21.1243,-8.1186,0;22.2321,-7.5166,0;23.7252,-19.028,0;

AuxInfo=1/1/N:52,24,90,40,41,50,100,60,51,23,61,68,66,67,17,16,83,65,64,15,81,30,28,84,92,37,62,99,74,71,13,45,11,39,49,22,59,63,9,88,79,31,35,95,98,75,70,42,76,25,5,47,19,56,77,86,78,26,34,93,7,6,53,18,55,44,85,2,48,12,91,10,80,33,14,38,96,73,69,94,43,58,21,1,27,32,3,4,89,87,82,29,36,97,8,72,54,20,57,46/E:(4,5)(13,14)(18,19)(85,86)(87,88)/it:im/rA:100cONOOCCCOCNCNCNCCCCCONCCCCCOCOCCONCCOCNCCCCNCCSCNCCCCCOCCONCCCCCCCCCCNCCONCCCCCCNCOCCNCOCOCNCCNCNOCCC/rB:;;;s3d4;;;d7;;s9;s10;d11;d9s12;;;;s15s16;s14;s18;d18;N19;s19;s22;s23;;s21;d25;s25;d26;s28;s26s30;s25;N31;s33;s34;d34;s35;N35;s37;s39;s39;;s42;d43;s42;s44s45;s44;s47;s47;s49;s49;s51;s38s42;d53;;s55;d55;P56;s56;s59;s59;;s62;d63;s63;d65;s64;s66d67;s7;s6p69;s5s70;d6;s6;;n73s74;d1s2s74;s75;s58;s78;N79;s79;d78;s81;s83;s84;s80;d86;p14s15s86;d77;s61;s77;s16s91;;s55;s62s93p94;s93;d93;s7n96;s9s98;s22;/rC:12.1656,-8.504,0;12.1656,-6.2884,0;16.5968,-3.1336,0;15.3445,-5.2769,0;16.5968,-4.5785,0;16.7654,-7.5166,0;20.0406,-7.5166,0;20.0406,-6.2402,0;22.208,-6.2161,0;23.2436,-5.4937,0;22.8582,-4.2895,0;21.6059,-4.2895,0;21.1725,-5.4937,0;19.294,-19.028,0;16.067,-19.6542,0;11.2264,-17.9202,0;13.1048,-19.6542,0;20.45,-18.426,0;21.5337,-19.028,0;20.45,-17.1255,0;21.5578,-21.1954,0;22.6174,-18.4019,0;22.6174,-17.1255,0;23.7252,-16.4512,0;19.2459,-23.9168,0;22.7137,-21.8698,0;19.2699,-25.2654,0;20.4018,-23.2425,0;23.8697,-21.1714,0;21.5819,-23.8927,0;22.7378,-23.1943,0;18.0899,-23.2665,0;23.9179,-23.8686,0;25.0497,-23.1702,0;26.2298,-23.8686,0;25.0497,-21.8457,0;27.3617,-23.1702,0;26.2298,-25.2172,0;27.3617,-21.8457,0;28.5417,-21.1714,0;26.2298,-21.1714,0;28.5417,-25.2172,0;29.8181,-25.6025,0;30.6128,-24.5188,0;28.5417,-23.8686,0;29.8181,-23.411,0;31.9614,-24.5188,0;32.6357,-25.6989,0;32.6357,-23.3629,0;31.9614,-22.2069,0;33.9603,-23.3629,0;34.6346,-24.5188,0;27.3617,-25.8675,0;27.3617,-27.2161,0;20.0165,-11.3457,0;18.9328,-11.9959,0;20.0165,-10.0452,0;18.9087,-13.3686,0;17.825,-11.3457,0;16.7172,-11.9959,0;17.825,-10.0693,0;23.5807,-11.7551,0;23.5807,-13.0315,0;24.7367,-13.6817,0;22.5211,-13.6817,0;22.5211,-14.9822,0;24.7367,-14.934,0;23.5807,-15.5842,0;18.9328,-8.1427,0;17.8009,-7.5166,0;17.8009,-5.2769,0;16.091,-6.3365,0;16.1633,-8.6003,0;14.0681,-7.3962,0;14.7906,-8.6003,0;12.8158,-7.3962,0;14.0681,-9.8044,0;17.5119,-13.3686,0;16.8135,-14.5728,0;17.5119,-15.7528,0;15.4408,-14.5728,0;17.0699,-12.6613,0;14.7665,-15.7528,0;13.3697,-15.7528,0;12.6713,-16.9569,0;16.8135,-16.9569,0;15.4408,-16.9569,0;17.5119,-18.137,0;14.7906,-10.9845,0;19.0291,-9.395,0;12.6954,-9.8044,0;11.2264,-11.1049,0;22.2321,-10.0452,0;21.1243,-11.9478,0;22.2321,-11.3457,0;21.1243,-9.4191,0;23.3399,-9.4191,0;21.1243,-8.1186,0;22.2321,-7.5166,0;23.7252,-19.028,0;

Who Has Responsibility? Who will take responsibility for drawing/enumerating the structures? Where can software contribute? What Quality is “good enough”? We MUST reduce rework!!!

Who will take responsibility for drawing/enumerating the structures?

Where can software contribute?

What Quality is “good enough”?

We MUST reduce rework!!!

A Lot of Variability in InChIs Source: Unofficial InChI FAQ page

Source: Unofficial InChI FAQ page

InChIs for Taxol

Taxol DrugBank: RCINICONZNJXQF-CLDWUXIMDD ChEBI: RCINICONZNJXQF-GXKQXQCDDN Wikipedia: RCINICONZNJXQF-MZXODVADBJ Which one is correct???

DrugBank: RCINICONZNJXQF-CLDWUXIMDD

ChEBI: RCINICONZNJXQF-GXKQXQCDDN

Wikipedia: RCINICONZNJXQF-MZXODVADBJ

Which one is correct???

InChIKeys for Taxol DrugBank: RCINICONZNJXQF-CLDWUXIMDD ChEBI: RCINICONZNJXQF-GXKQXQCDDN Wikipedia: RCINICONZNJXQF-MZXODVADBJ ChEBI and Wikipedia are the SAME structure Drugbank is a DIFFERENT structure at ONE stereocenter

DrugBank: RCINICONZNJXQF-CLDWUXIMDD

ChEBI: RCINICONZNJXQF-GXKQXQCDDN

Wikipedia: RCINICONZNJXQF-MZXODVADBJ

ChEBI and Wikipedia are the SAME structure

Drugbank is a DIFFERENT structure at ONE stereocenter

Does one stereocenter matter? Distaval, Talimol, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, and Softenon

Distaval, Talimol, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, and Softenon

InChIStrings Hash to InChIKeys

The InChI Resolver

HVYWMOMLDIMFJA-DPAQBDIFSA-N

Resolve-It

Resolve-It

Pretty-It

JMol-It, Download-It and Zoom-It

Kind-of-Resolve-It

Generate-It

Draw-It : Thanks Symyx (Beta release)

Generate-It

All Flavors

Serve Up Services

And Once It’s Resolved…

Out to ChemSpider…and its resources

COMING: InChI Resolver to DOIs

Full Text-Based Literature Searching to DOIs Including Citations Now

When Structures are “Connected”

When Structures are “Connected”

ChemSpider Everywhere Linked from Wikipedia Linked from Open Notebook Science sites using EMBED Linked from Blogs using Structure/Spectra EMBED Integrated into structure drawing packages such as ACD/ChemSketch, Symyx Draw, Open Source applets Integrated to software offerings from Thermo, Waters, Agilent, Bruker

Linked from Wikipedia

Linked from Open Notebook Science sites using EMBED

Linked from Blogs using Structure/Spectra EMBED

Integrated into structure drawing packages such as ACD/ChemSketch, Symyx Draw, Open Source applets

Integrated to software offerings from Thermo, Waters, Agilent, Bruker

ChemSpider Everywhere Embed Functionality (like YouTube)

ChemSpider Everywhere www.spectralgame.com

ChemSpider Everywhere Crowdsourced Curation of Spectra

ChemSpider Everywhere RSC Compounds

ChemSpider Everywhere Nature Chemistry Nature Chemistry articles are annotated to identify all of the chemical compounds mentioned throughout the text. Users can choose to view the article with all of the compounds highlighted, and find out more about those compounds by linking out to other information resources including PubChem and ChemSpider .

Nature Chemistry articles are annotated to identify all of the chemical compounds mentioned throughout the text. Users can choose to view the article with all of the compounds highlighted, and find out more about those compounds by linking out to other information resources including PubChem and ChemSpider .

ChemSpider Everywhere ChemMobi

Structure RSS Feeds with InChIs

InChIs are Incomplete What is NOT supported, yet: polymers organometallics Markush structures 3-D structures excited states interlocking structures (e.g. rotaxanes) host-guest complexes

What is NOT supported, yet:

polymers

organometallics

Markush structures

3-D structures

excited states

interlocking structures (e.g. rotaxanes)

host-guest complexes

Progressing InChI Highest priority for the InChI Team is communication with structure drawing package vendors – THE interfaces to the users For the InChI Resolver : Delivery of services to allow publishers to deposit their structure collections with associated DOIs to ChemSpider Not every structure is important…Discussions with Publishers to discern primary compounds

Highest priority for the InChI Team is communication with structure drawing package vendors – THE interfaces to the users

For the InChI Resolver : Delivery of services to allow publishers to deposit their structure collections with associated DOIs to ChemSpider

Not every structure is important…Discussions with Publishers to discern primary compounds

Conclusions InChIs and Internet Chemistry http://inchis.chemspider.com

InChIs and Internet Chemistry

http://inchis.chemspider.com

Acknowledgments Richard Kidd, Royal Society of Chemistry Keith Taylor, Symyx Chris Singleton, Steven Bachrach and Alan McNaught for feedback “ The InChI team”

Richard Kidd, Royal Society of Chemistry

Keith Taylor, Symyx

Chris Singleton, Steven Bachrach and Alan McNaught for feedback

“ The InChI team”