acs san diego, march 2012, inchi symposium

Accessing NCI/CADD Web Resources by InChI

Markus SitzmannComputer-Aided Drug Design Group, Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, NIH, DHHS

http://cactus.nci.nih.gov

Chemical Identifier Resolver (CIR)

http://cactus.nci.nih.gov/chemical/structure

CIR works as a resolver for different chemical structure identifiers orrepresentations. It allows one to convert a givenstructure identifier into anotherrepresentation or structureidentifier.

Chemical Structure Representations

chemical structureNCI/CADD Identifiers

InChI/InChIKey

ChemSpider ID

PubChem SID/CID

chemical names

CAS Registry Number

NSC number

FDA UNII

ChemNavigator SID

SMILES

SD File

Chemical FormulaChEBI ID

PDB Ligand ID

MRV

CML

SYBYL Line Notation

GIF image

Chemical Structure Representations

InChINCI/CADD Identifiers

InChI/InChIKey

ChemSpider ID

PubChem SID/CID

chemical names

CAS Registry Number

NSC number

FDA UNII

ChemNavigator SID

SMILES

SD File

Chemical FormulaChEBI ID

PDB Ligand ID

MRV

CML

SYBYL Line Notation

GIF image

many more …

Chemical Structure Databases

InChI



CIR works as a resolver for different chemical structure identifiers orrepresentations. It allows one to convert a givenstructure identifier into anotherrepresentation or structureidentifier.



Works as a resolver for different chemical structure identifiers. Allows one to convert a givenstructure identifier into anotherrepresentation or structureidentifier.

C7H6O2APtclcactv03051222202D 0 0.00000 0.00000 15 15 0 0 0 0 0 0 0 0999 V2000 2.8660 -2.0600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7321 -1.5600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7321 -0.5600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8660 -0.0600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 -0.5600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 -1.5600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8660 0.9400 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7321 1.4400 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 1.4400 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8660 -2.6800 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2690 -1.8700 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2690 -0.2500 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4631 -0.2500 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4631 -1.8700 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7321 2.0600 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 0 0 0 2 3 1 0 0 0 0 3 4 2 0 0 0 0 4 5 1 0 0 0 0 5 6 2 0 0 0 0 1 6 1 0 0 0 0 4 7 1 0 0 0 0 7 8 1 0 0 0 0 7 9 2 0 0 0 0 1 10 1 0 0 0 0 2 11 1 0 0 0 0 3 12 1 0 0 0 0 5 13 1 0 0 0 0 6 14 1 0 0 0 0 8 15 1 0 0 0 0M END$$$$SD file

ChemWriter Editor

WPYMKLBDIGXBTP-FZOZFQFYNA-N




benzoic acid65-85-0WLN: QVRUnisept BZAAIDS018010Salvo liquidBenzoic acid-ring-UL-14CST5213864BenzoesaeureCHEBI:30746NSC 149benzenecarboxylic acidphenylformic acidBenzoic acid (JP15/USP)Benzoic acid (TN)18102_RIEDELAromatic hydroxy acidBenzoic acid (7CI,8CI,9CI)Benzoic acid [USAN:JAN]W213128_ALDRICH47849_SUPELCOAcide benzoique [French]Acido benzoico [Italian]Benzoate (VAN)Benzoesaeure [German]Benzoic acid (natural)Acide benzoiqueBenzeneformic acidBenzenemethanoic acidBenzoesaeure GKBenzoesaeure GVBenzoic acid, tech.CarboxybenzeneKyselina benzoovaPhenylcarboxylic acidnames

ChemWriter Editor





InChIKey=WPYMKLBDIGXBTP-UHFFFAOYSA-NInChI=1S/C7H6O2/c8-7(9)6-4-2-1-3-5-6/h1-5H,(H,8,9)C1=CC=C(C=C1)C(O)=O

ChemWriter Editor


InChIKeyInChI

SMILES


programmatic URL API:

http://cactus.nci.nih.gov/chemical/structure/”identifier”/”representation”

if a request is not successful: HTTP404 status message


programmatic URL API:

http://cactus.nci.nih.gov/chemical/structure/”identifier”/”representation”

if a request is not successful: HTTP404 status message

http://cactus.nci.nih.gov/chemical/structure/PGZUMBJQJWIWGJ-ONAKXNSWSA-N/cas

204255-11-8 MIME type: text/plain

examples:

http://cactus.nci.nih.gov/chemical/structure/PGZUMBJQJWIWGJ-ONAKXNSWSA-N/image

MIME type: image/gif


• access by programming libraries/languages (e.g. Python):

• access from Unix shell level (e.g., via wget):

shell > wget -qO - \http://cactus.nci.nih.gov/chemical/structure/tamiflu/cas204255-11-8

from urllib2 import *url = “http://cactus.nci.nih.gov/chemical/structure/tamiflu/cas”resolver = urlopen(url) try:

response = resolver.read() except HTTPError:

raise “your own error handling”print response204255-11-8

InChI/InChIKey(trivial) names

CAS Registry numbers

IUPAC names (OPSIN)

structure images(GIF, PNG)

chemical properties(MW, formula, …)

Database RegIDs(PubChem, ZINC, eMolecules, ChemSpider ID)

structure files (sdf, pdb, cdx, …)

SMILES

Chemical Identifier Resolver: InChI/InChIKey

CIR

chemical namesIUPAC names (OPSIN)

CAS numbersSMILES strings

IUPAC InChI/InChIKeysNCI/CADD Identifiers

CACTVS HASHISYNSC number

PubChem SIDZINC Code

ChemSpider IDChemNavigator SID

eMolecule VID

/smiles/names, /iupac_name/cas/inchi, /stdinchi/inchikey, /stdinchikey/ficts, /ficus, /uuuuu /image/file, /sdf/mw, /monoisotopic_mass /formula/twirl/urls/chemspider_id/pubchem_sid/chemnavigator_sid

“identifier” “representation”

http://cactus.nci.nih.gov/chemcial/structure

CIR


identifier representation

http request

http response

detection ofthe identifier

type

detection ofthe identifier

type

identifier is afull structure

representation(e.g. SMILES, InChI)

calculation of therequested structure

representation

calculation of therequested structure

representation

identifier is ahashed structure

representation(e.g. InChIKey),

chemical name etc.

database lookup

MIME type

structure

e.g. InChI, GIF image

e.g. CAS number,chemical name


CSDB

Chemical Structure Database (CSDB)

• ChemNavigator iResearch Librarycompilation of commercially available screeningcompounds from ~300 international chemistrysuppliers

• PubChem databaseincluding Open NCI database, EPA DSSTox databases, NIAID HIV database, NIST Webbook, NLM ChemIDplus, ChemSpider, …

• Commercial Sources / othersAsinex, Comgenex, eMolecules, …

ChemNav.iResearch Lib.~56%

PubChem~38%

others

~6%

140 chemical structure databases120 million structure records

84.6 million unique structures by FICuS110 million Standard InChIKeys for lookup

current status: (as of March 2010)

• PubChem Substance & Compound as separate databases(both updated to 2012)

• ChemNavigator iResearch Library: updated to 2012• new databases, e.g.

• Therapeutic Target Database (TTD) • Human Metabolome Database (HMDB)• DrugBank

• “pull” download of databases also available in PubChem, e.g.• DSSTox, ZINC 2012/01, ChEBI 2012/01, ChEMBL13,

ChemIDplus 2012/01• to a limited extend “historic versions” of databases are archived,

e.g. comparison of PubChem Substance 2007 vs 2012 will be possible

Chemical Structure Database (Update 2012)


Chemical Structure Normalization

• calculation of a set of parent structures with differentsensitivity to chemical features:

structurenormalization

parentstructure

NCI/CADDIdentifier

hashcodecalculation

E_HASHISYFICTS

original structure

record

FICuS

uuuuu

MolfileSDFSMILESChemDraw cdxPDB

SDFSMILESdatabase

both the original structure record & the normalized parent structuresare archived in the database


NCI/CADD Identifiers (FICTS, FICuS, uuuuu)

HNN NH2

O-

ONa+

6C16DE2351F9FF50-FICTS

NNH NH2

OH

O

9850FD9F9E2B4E25-FICTS

HNN

OH

O

NH2HN

NOH

O

NH2HN

N NHOH

O

E92E4BA2869F3611-FICTS 8A7AD1EB498CC76A-FICTS

E92E4BA2869F3611-FICuS 8A7AD1EB498CC76A-FICuSE5F83F10C5DB080A-FICuS

E5F83F10C5DB080A-FICTS

9850FD9F9E2B4E25-uuuuu

9850FD9F9E2B4E25-FICuS

tautomer salt SRhistidine:

structure normalization:

based on CACTVS hashcodes (HASHISY)16-digit hexadecimal number (64-bit unsigned) HN

N NH2

OH

O

9850FD9F9E2B4E25

HNN NH2

O-

ONa+

6C16DE2351F9FF50-FICTS

NNH NH2

OH

O

9850FD9F9E2B4E25-FICTS

HNN

OH

O

NH2HN

NOH

O

NH2HN

N NHOH

O

E92E4BA2869F3611-FICTS 8A7AD1EB498CC76A-FICTS

E92E4BA2869F3611-FICuS 8A7AD1EB498CC76A-FICuSE5F83F10C5DB080A-FICuS

E5F83F10C5DB080A-FICTS

9850FD9F9E2B4E25-uuuuu

9850FD9F9E2B4E25-FICuS

tautomer salt SRhistidine:

structure normalization:

based on CACTVS hashcodes (HASHISY)16-digit hexadecimal number (64-bit unsigned) HN

N NH2

OH

O

9850FD9F9E2B4E25


FICTS

FICuS

uuuuu

~118 million

~115 million

~100 million

231 small-molecule database367 database releases (full, incremental, “historic versions”)324 million original database records


Unique structure count:


InChI/InChIKey

InChI/InChIKey (Version 1.04) calculated with four InChI flag sets:

Set 1

Set 2

Set 3

Standard Standard InChIKey

DONOTADDH W0 FIXEDH RECMET NEWPS SPXYZ SAsXYZ Fb Fnud KET 15T



Add H

Add H

Add H

Add H

CACTVS

:

:

:

:

Standard Set, Set 1 & Set 2: addition of hydrogen atoms by CACTVSSet 3: addition of hydrogen atoms by the InChI library

structurenormalization

parentstructure

NCI/CADDIdentifier

hashcodecalculation

E_HASHISYFICTS

original structure

record

FICuS

uuuuu


InChI/InChIKey

• calculation of InChI/InChIKey Standard set, Set 1, Set 2 & Set 3for all original structure records and normalized parent structure:

Set 1 Set 2 Set 3Standard

InChI/InChIKey

Using CIR with InChI/InChIKey


(Partial) InChIKey Lookup

http://cactus.nci.nih.gov/chemical/structure/LFQSCWFLJHTTHZ-UHFFFAOYSA-N/smiles

CCO

http://cactus.nci.nih.gov/chemical/structure/LFQSCWFLJHTTHZ-UHFFFAOYSA/smiles`

CCOCC[OH2+]

http://cactus.nci.nih.gov/chemical/structure/LFQSCWFLJHTTHZ/smiles

C(C(O)([2H])[2H])[2H]CC(O)([2H])[2H]C(CO)([2H])([2H])[2H]CC[17OH]C(CO)[2H][14CH3]COCCO

• resolve Standard InChIKey into full structure representation: Ethanol


Chemical File Representation

• available file format representations:

alc Alchemy formatcdxml CambridgeSoft ChemDraw XML formatcerius MSI Cerius II formatcharmm Chemistry at HARvardMacromolecular Mechanics file formatcif Crystallographic Information Filecml Chemical Markup Languagegjf Gaussian input data filegromacs GROMACS file formathyperchem HyperChem file formatjme Java Molecule Editor format

maestro Schroedinger MacroModelstructure file formatmol Symyx molecule filesybyl2/mol2 Tripos Sybyl MOL2 formatmrv ChemAxon MRV formatpdb Protein Data Banksdf Symyx Structure Data Formatsdf3000 Symyx Structure Data Format 3000sln SYBYL Line Notationsmiles SMILESxyz xyz file format

http://cactus.nci.nih.gov/chemical/structure/BSYNRYMUTXBXSQ-UHFFFAOYSA-N/file?format=sdfAspirin


Chemical Structure Images (GIF, PNG)

http://cactus.nci.nih.gov/chemical/structure/XMWRBQBLMFGWIX-UHFFFAOYSA-N/image?height=300&width=300&bgcolor=black&bondcolor=white

http://cactus.nci.nih.gov/chemical/structure/BSYNRYMUTXBXSQ-UHFFFAOYSA-N/image?height=200&width=200&symbolfontsize=7&footer="Aspirin"

Buckyball

Aspirin


3D Chemical Structure Visualization (TwirlyMol)

implemented by Noel O'Boyle (University College Cork, Ireland)

Chrome Safari FF3.6+ IE9 IE8 IE7 IE6

simple javascript that allows you to render a rotatable/zoomable3D representation of a molecule in your web browser

no plugin is needed, only a modern browser:

simple viewer:http://cactus.nci.nih.gov/chemical/structure/DDPJWUQJQMKQIF-XPNZOOHZSA-N/twirl

embedded into a web page:

<div id=“canvas” height=“400” width=“400”></div><script src=“http://cactus.nci.nih.gov/chemical/structure/

DDPJWUQJQMKQIF-XPNZOOHZSA-N/twirl_cached/canvas” />



Restasis

http://www.coronene.com/blog/

http://chemical-quantum-images.blogspot.com

http://baoilleach.blogspot.com/




Chemical Database URLs

<?xml version="1.0" encoding="UTF-8" ?> <request string="DDPJWUQJQMKQIF-XPNZOOHZSA-N" representation="urls">

<data id="1" resolver=“stdinchikey" string_class=“Standard InChIKey"><item id="1" classification="exact" database="ChemSpider" publisher="ChemSpider">

http://chemspider.com/structure.4939506</item><item id="2" classification="exact" database="ChemSpider“ publisher="PubChem">

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=43028058</item><item id="3" classification="exact" database="NLM ChemIDplus" publisher="NLM">

http://chem.sis.nlm.nih.gov/chemidplus/direct.jsp?result=advanced&regno=059865133[…]

</data></request>

• request database URLs:

http://cactus.nci.nih.gov/chemical/structure/DDPJWUQJQMKQIF-XPNZOOHZSA-N/urls/xmlRestasis


Chemical Name Lookup

• request (alternative) names:

<?xml version="1.0" encoding="UTF-8" ?> <request string=“BSYNRYMUTXBXSQ-UHFFFAOYSA-N" representation="names">

<data id="1" resolver=“stdinchikey" string_class=“Standard InChIKey"><item id="1" classification=“pubchem_iupac_name">2-acetyloxybenzoic acid</item><item id="2" classification="pubchem_iupac_openeye_name">2-Acetoxybenzoic acid</item><item id="3" classification="pubchem_generic_registry_name">50-78-2</item><item id="4" classification="pubchem_generic_registry_name">11126-35-5</item><item id="5" classification="pubchem_generic_registry_name">11126-37-7</item><item id="6" classification="pubchem_generic_registry_name">2349-94-2</item><item id="7" classification="pubchem_generic_registry_name">26914-13-6</item><item id="8" classification="pubchem_substance_synonym">NCGC00090977-04</item><item id="9" classification="pubchem_substance_synonym">KBioSS_002272</item><item id="10" classification="pubchem_substance_synonym">SBB015069</item><item id="11" classification="pubchem_substance_synonym">Aspirin</item><item id="12" classification="pubchem_substance_synonym">D00109</item>

[…]

http://cactus.nci.nih.gov/chemical/structure/BSYNRYMUTXBXSQ-UHFFFAOYSA-N/names/xmlAspirin


Chemical Properties

• request molecular weight:

http://cactus.nci.nih.gov/chemical/structure/BSYNRYMUTXBXSQ-UHFFFAOYSA-N/weight

180.1598

/mw molecular weight/formula formula/monoisotopic_mass monoisotopic mass/h_bond_donor_count H bond donor count/h_bond_acceptor_count H bond acceptor count/h_bond_center_count H bond center count/rotor_count number of rotatable bonds/effective_rotor_count number of effectively rotatable bonds/rule_of_5_violation_count number of Rule-of-5 violations/xlogp2 octanol−water partition coefficient XLOGP2

/aromatic compound is aromatic/macrocyclic compound is macrocyclic/heteroatom_count heteroatom count/hydrogen_atom_count H atom count/heavy_atom_count heavy atom count/deprotonable_group_count number of deprotonable groups/protonable_group_count number of protonable groups/ring_count number of rings/ringsys_count number of ringsystems

MIME type: text/plain

Aspirin

example: all chemical names that contain the words “morphine” and “methyl”(name pattern: ‘+morphine +methyl‘):

http://cactus.nci.nih.gov/chemical/structure/+morphine +methyl/stdinchikey/xml?resolver=name_pattern


Chemical Name Pattern Search

based on the open sourcefull text search server Sphinx(http://sphinxsearch.com)

• Google-like searches on CIR’s name index (approx. 70 million names)

<request string="+morphine +methyl" representation="stdinchikey"><data id="1" resolver="name_pattern" notation="Morphine 3-methyl ether">

<item id="1">InChIKey=OROGSEYTTFOCAN-DNJOTXNNSA-N</item></data><data id="2" resolver="name_pattern" notation="6-Methyl-delta(sup 6)-deoxy-morphine">

<item id="1">InChIKey=CUFWYVOFDYVCPM-GGNLRSJOSA-N</item></data><data id="3" resolver="name_pattern" notation="Morphine, dihydro-6-methyl-">

<item id="1">InChIKey=NBKVWIJQJMEQLE-NGTWOADLSA-N</item></data><data id="4" resolver="name_pattern“ notation="6-METHYL-MORPHINE ETHER">

<item id="1">InChIKey=FNAHUZTWOVOCTL-UHFFFAOYSA-N</item></data><data id="5" resolver="name_pattern" notation="Morphine alcoholic methyl ether">

<item id="1">InChIKey=FNAHUZTWOVOCTL-XSSYPUMDSA-N</item></data><data id="6" resolver="name_pattern" notation="N-Methyl morphine chloride">

<item id="1">InChIKey=MJNCZWBHCFTYFU-SCLAZZCHSA-N</item></data><data id="7" resolver="name_pattern" notation="Morphine, 7-hydroxy-6,6-dimethoxy-3-O-methyl-">

<item id="1">InChIKey=URFKRBIESURBKC-UHFFFAOYSA-N</item></data>

</request>

Search name pattern ‘+morphine +methyl’: 7 matching names


Chemical Name Pattern Search

example: chemical names that contain the words “morphine” and “methyl”but not “hydroxyl” (name pattern: ‘+morphine +methyl -hydroxyl‘): http://cactus.nci.nih.gov/chemical/structure/+morphine +methyl -hydroxyl/stdinchikey/xml?resolver=name_pattern

example: chemical names that contain the substring “morphine”somewhere in the name (name pattern: ‘*morphine*‘) http://cactus.nci.nih.gov/chemical/structure/*morphine*/stdinchikey/xml?resolver=name_pattern

example: chemical names that contain a single character “m” and the word “benzene” in a maximum distance of 3 words (finds meta-substituted aromaticcompounds, name pattern: ‘“m benzene”~3‘):http://cactus.nci.nih.gov/chemical/structure/(m benzene)~3/stdinchikey/xml?resolver=name_pattern

6 matching names

45 matching names

22 matching names

Structure Normalization(Tautomerism)

Structure Normalization

Tautomerism

rule 12: furanones

rule 11: 1.11 (aromatic) heteroatom H shiftrule 10: 1.9 (aromatic) heteroatom H shiftrule 9: 1.7 (aromatic) heteroatom H shiftrule 8: 1.5 aromatic heteroatom H shift (2)rule 7: 1.5 (aromatic) heteroatom H shift (1)rule 6: 1.3 heteroatom H shiftrule 5: 1.3 aromatic heteroatom H shiftrule 4: special iminerule 3: simple (aliphatic) iminerule 2: 1.5 (thio)keto/(thio)enolrule 1: 1.3 (thio)keto/(thio)enol

21 SMIRKS transform rules:

rule 21: phosphonic acidsrule 20: isocyanidesrule 19: formamidinesulfinic acidsrule 18: cyanic/iso-cyanic acidsrule 17: oxim/nitroso via phenolrule 16: oxim/nitrosorule 15: pentavalent nitro/aci-nitrorule 14: ionic nitro/aci-nitro

rule 13: keten/ynol exchange


Tautomerism

[O,S,Se,Te;X1:1]=[C;z{1-2}:2][CX4R{0-2}:3][#1:4]>>[#1:4][O,S,Se,Te;X2:1][#6;z{1-2}:2]=[C,cz{0-1}R{0-1}:3]

[N,n,S,s,O,o,Se,Te:1]=[NX2,nX2,C,c,P,p:2][N,n,S,O,Se,Te:3][#1:4]>>[#1:4][N,n,S,O,Se,Te:1][NX2,nX2,C,c,P,p:2]=[N,n,S,s,O,o,Se,Te:3]

32

O1

H 43

2O1H 4

N2

S1 N 3

H

H4

HN2

S1 N3

H

H4

H

1.3 keto/enol

1.3 heteroatom H shift

rule 1: 1.3 (thio)keto/(thio)enol

rule 6: 1.3 heteroatom H shift


Warfarin - Tautomers

HO

O

O

HO

O

O

O

HO

O

O

O

O

O

O

OH

O

HO

O

O

O

HO

O

OH

O

HO

O

OH

O

HO

O

O

O

HO

O

O

HO

prototropic tautomerism


Warfarin - Tautomers

HO

O

O

HO

O

O

O

HO

O

O

O

O

O

O

OH

O

HO

O

O

O

HO

O

OH

O

HO

O

OH

O

HO

O

O

O

HO

O

O

HO

http://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/representationhttp://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/representation


D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS D76B88C0354759F1-FICuS





Warfarin – FICuS Identifier FICuS

http://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/ficushttp://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/ficus


HO

O

O

HO

O

O

O

HO

O

O

O

O

O

O

OH

O

HO

O

O

O

HO

O

OH

O

HO

O

OH

O

HO

O

O

O

HO

O

O

HO




09BB2FAADA1508A7-FICuS

09BB2FAADA1508A7-FICuS

2F505A3FCA434B3C-FICuS

ring-chaintautomerism prototropic tautomerism


Warfarin – FICuS Identifier FICuS

http://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/ficushttp://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/ficusring-chain

tautomerism prototropic tautomerism

HO

O

O

HO

O

O

O

HO

O

O

O

O

O

O

OH

O

HO

O

O

O

HO

O

OH

O

HO

O

OH

O

HO

O

O

O

HO

O

O

HO

O

OH

OHO

O

O

OHO

O

O

O

HO


Warfarin –

QTXVAVXCBMYBJW-UHFFFAOYSA-N VWSXIGYSLWNCBN-VAWYXSNFSA-N GRAAPKVUSREWIL-UHFFFAOYSA-N

FQEPJUOLUDFINX-UHFFFAOYSA-N UCKRWKACBKRIKB-VAWYXSNFSA-N NNLYDNMZCAHUOV-UHFFFAOYSA-N

PJVWKTKQMONHTI-UHFFFAOYSA-N FVSFCRPKSVCTBA-VAWYXSNFSA-N BBOSKMPTDUUMKL-UHFFFAOYSA-N

LSCYDZJASSKSMJ-UHFFFAOYSA-N

XGIOTBZTMHLTRL-UHFFFAOYSA-N

QUJJIKXCACZKKD-UHFFFAOYSA-N

Standard InChIKey

ring-chaintautomerism


http://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/stdinchikeyhttp://cactus.nci.nih.gov/chemical/structure/tautomers:warfarin/stdinchikey

HO

O

O

HO

O

O

O

HO

O

O

O

O

O

O

OH

O

HO

O

O

O

HO

O

OH

O

HO

O

OH

O

HO

O

O

O

HO

O

O

HO

O

OH

OHO

O

O

OHO

O

O

O

HO


Warfarin –

SAYISSDYYDIVTP-UHFFFAOYNA-N SAYISSDYYDIVTP-UHFFFAOYNA-N PMOPDASZKFXBOL-UHFFFAOYNA-N



LSCYDZJASSKSMJ-UHFFFAOYNA-N

FQOKLKCGRHFANU-UHFFFAOYNA-N

FQOKLKCGRHFANU-UHFFFAOYNA-N

InChIKey (W0 RECMET NEWPS SPXYZ SAsXYZ Fb Fnud KET 15T) InChIKey (W0 RECMET NEWPS SPXYZ SAsXYZ Fb Fnud KET 15T)ring-chain

tautomerism prototropic tautomerism

HO

O

O

HO

O

O

O

HO

O

O

O

O

O

O

OH

O

HO

O

O

O

HO

O

OH

O

HO

O

OH

O

HO

O

O

O

HO

O

O

HO

O

OH

OHO

O

O

OHO

O

O

O

HO

InChIKey


Warfarin

MIME type: text/plain

• “normalize” Standard InChIKey by NCI/CADD’s business rules:

http://cactus.nci.nih.gov/chemical/structure/normalize:QTXVAVXCBMYBJW-UHFFFAOYSA-N/stdinchikey

InChIKey=FQEPJUOLUDFINX-UHFFFAOYSA-N

O

O

O

HO

O

O

O

O

FQEPJUOLUDFINX-UHFFFAOYSA-N QTXVAVXCBMYBJW-UHFFFAOYSA-N

add_hyrogens, remove_hydrogens, normalize, ficts, ficus, uuuuu,scaffold_sequence, nostereo, stereoisomers, tautomers

• available operators:

http://cactus.nci.nih.gov/chemical/structure/scaffold_sequence:FQEPJUOLUDFINX-UHFFFAOYSA-N/stdinchikey

O

O

O


Chemical Operators

O

O

O O

O

O

XVYBSGQBRUYLNK-UHFFFAOYSA-N BQLSCAPEANVCOG-UHFFFAOYSA-N MERGMNQXULKBCH-UHFFFAOYSA-N

example:

Schuffenhauer et al., J. Chem. Inf. Model. 2007, 47, 47-58

Soon: Chemical File Resolver (CFR)

Chemical File Resolver (CFR)

CFRchemical

fileHTTP Post HTTP Getchemical

file

• allows conversion of many chemical file formats into another format or other representations

• will have a programmatic URL API & a HTML Web interface• url’izes all elements of the original file, i.e. provides access to each

specific record, field, and any metadata (size, record count, etc.) of the posted file by URLs

• release: Q2/2012 (hopefully)

HTTP Post


curl -F upload=@/your/local/file.sdf http://cactus.nci.nih.gov/chemical/file>d85b396ed6ced6348a5b402eb8fcfe8b

• HTTP: post a file (e.g. with curl), CFR replies with a MD5 hash key:

• accepted formats:• chemical file formats: alc, cdxml, cerius, charmm, cif, cml, jme,

maestro, mol, mol2, mrv, pdb, sdf, sdf3000, sln, smiles, xyz, …• text files with a list of identifiers …

CFRchemical

fileHTTP Getchemical

file

HTTP PostCFR

chemical file

HTTP Getchemical file

Post a plain text file, e.g.:

curl -F upload=@/your/local/file.sdf http://cactus.nci.nih.gov/TEST/chemical/file>d85b396ed6ced6348a5b402eb8fcfe8b

• after posting a file, CFR replies with a MD5 hash sum:

• accepted formats:• chemical file formats: alc, cdxml, cerius, charmm, cif, cml, jme,

maestro, mol, mol2, mrv, pdb, sdf, sdf3000, sln, smiles, xyz, …• text files with a list of identifier:

ethanolaspirinInChI=1S/C4H10O/c1-3-5-4-2/h3-4H2,1-2H3CCOCCInChIKey=RCINICONZNJXQF-MZXODVADSA-NInChIKey=QTXVAVXCBMYBJW-UHFFFAOYSA-N 204255-11-8 tautomers:guanineChemSpider_ID=1234Pubchem_SID=456


CFRchemical


file

• request new file format using the obtained MD5 hash key:

curl http://cactus.nci.nih.gov/TEST/chemical/file/{key}?format={sdf, smi, pdb, cml, …}

d85b396ed6ced6348a5b402eb8fcfe8b


CFRchemical


file

• request record 2 and 5 as SMILES string:

curl http://cactus.nci.nih.gov/TEST/chemical/file/{key}?records=2,5&format=smiles

d85b396ed6ced6348a5b402eb8fcfe8b


CFRchemical


file

• get field names:

curl http://cactus.nci.nih.gov/TEST/chemical/file/{key}/fields

• get a specific field value from record n:

curl http://cactus.nci.nih.gov/TEST/chemical/file/{key}/n/{field_name}

Chemical Structure Web API

ChemicalFile

Resolver

NCI/CADDweb service

NCI/CADD Chemical StructureDatabase (CSDB)

CACTVS

externalweb services

http

ChemicalIdentifierResolver

othersoftwarepackages

Chemical Structure Web API

OPSIN

IUPAC InChI/InChIKey Resolver

• (hopefully) there will be many resolvers from differentproviders with different background:• publishers

• commercial databases

• free sources and databases: ChemSpider, PubChem, ChEBI, …

• InChI/InChIKey is the perfect tool to interlink the resolvers

• ChemSpider, PubChem and NCI/CADD are working on a test protocol for a federated InChI/InChIKey resolver

IUPAC InChI/InChIKey Resolver

IUPAC Root Resolver

Resolver 1

Resolver 2

Resolver 3

Resolver 3.1

Resolver 3.2

Resolver 3.3

ClientsCIR

Resolver 3

http://cactus.nci.nih.gov

http://cactus.nci.nih.gov/blog

Acknowledgments

The InChI Team

Xemistry GmbH, GermanyWolf-Dietrich Ihlenfeldt

All Database providers ChemNavigatorScott HuttonTad Hurst

University of Cambridge, UKDaniel Lowe

NCI/CADD TeamIgor FilippovMarc Nicklaus

University College Cork, IrelandNoel O’ Boyle

Acknowledgments - Software

CACTVS

Python Web FrameworkChemWriter

Python SQL Library

Javascript library

Peter Ertl (Novartis)

Fulltext Search Engine

acs san diego, march 2012, inchi symposium

Business

o structure identifier

riedel structure identifier

structure benzoic acid

givenstructure identifier

supelco identifier

chemical biology laboratory

given benzoic acid tn

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