ZINC15:examples:public

Level 1 questions - one-liners, using webpage

Ligands for Dopamine D2 receptor, and those you can buy on the second line, and those you can get in 2 weeks on the third

http://zinc15.docking.org/genes/DRD2/substances
http://zinc15.docking.org/genes/DRD2/substances/subsets/for-sale
http://zinc15.docking.org/genes/DRD2/substances/subsets/now

All available genes, those for which you can buy ligands, and just the viral genes where you can get ligands in 2 weeks.

http://zinc15.docking.org/genes
http://zinc15.docking.org/genes/having/substances/subsets/for-sale
http://zinc15.docking.org/genes/subsets/bacterial/having/substances/subsets/now

How many ChEMBL targets have at least one purchasable compound for sale?

http://zinc15.docking.org/targets/having/substances/subsets/for-sale/

How many ligands for ligand gated ion channels are for sale?

http://zinc15.docking.org/subclasses/lgic/substances/subsets/for-sale

What is the nearest metabolite or drug to my compound?

zinc15.docking.org/substances?ecfp4_fp=<url-encoded-smiles>

thus for ZINC27, using 0.4 as cutoff

http://zinc15.docking.org/substances?ecfp4_fp-tanimoto-0.4=27

and for phenol aka c1ccccc1O, using Dice, 50 cutoff instead of Tanimoto (must be URL encoded, see dencoder

http://zinc15.docking.org/substances?ecfp4_fp-dice-50=c1ccccc1O

Which FDA approved drugs are also metabolites?
http://zinc15.docking.org/substances/subsets/metabolites+fda

Which compounds are in Drugbank but not in ChEMBL Drugstore?

write me here ???

Which FDA approved drugs are associated with publications describing direct binding ligand affinity data:

http://zinc15.docking.org/substances/subsets/fda/having/references/

Which genes have a ligand reported that binds at 10nM concentration or better?

http://zinc15.docking.org/activities.txt:gene.name?activities.affinitynm:ge=8&distinct=gene.name&count=all

Which targets do hydroxamic acids bind to?

http://zinc15.docking.org/targets.txt:target.uniprot?structure.contains=C(=O)[ND2][OD1]&distinct=target.uniprot&count=all

Which vendors sell the most biogenic compounds (natural products), and what are those compounds?

http://zinc15.docking.org/catitms.txt:catalog.short_name,catitm.supplier_code,substance.zinc_id,substance.smiles?catalog.np=1&count=all

How many primary amines as for sale in preparative quantitites?

http://zinc15.docking.org/substances.txt?substance.structure:contains=[ND1]&catalog.bb=True&count=all

World drugs with no gene target annotated and no SEA prediction

http://zinc15.docking.org/substances/subsets/world/having/no-genes+no-predictions/

In-man compounds having no annotations in ChEMBL but DO have SEA predictions

http://zinc15.docking.org/substances/subsets/in-man/having/no-genes+predictions/

World drugs having no annotations, 10uM or better

http://zinc15.docking.org/substances/subsets/world/having/no-genes/

World drugs containing indole and having no genes annotated:

http://zinc15.docking.org/rings/indole/substances/subsets/world/having/no-genes/

World drugs having one or more PAINS patterns:

http://zinc15.docking.org/substances/subsets/world/having/patterns/subsets/pains/?sort=no

Aggregators that have been in clinical trials:

http://zinc15.docking.org/substances/subsets/aggregators/having/trials/

Endogenous human metabolites that have PAINS patterns (lots of incorrectly curated, please tell the source databases)

http://zinc15.docking.org/substances/subsets/endogenous/having/patterns/subsets/pains/?sort=no 

Compounds of biological origin that are also FDA approved drugs:

http://zinc15.docking.org/substances/subsets/fda+biogenic/

Biogenic compounds that hit phosphatase targets

http://zinc15.docking.org/subclasses/phosphatase/substances/subsets/biogenic/

Biogenic compounds that hit a GPCR-A target and are predicted for one or more ion channels using SEA:

http://zinc15.docking.org/substances/subsets/biogenic/?genes-any-sub_class_name=GPCR-A&predictions-any-major_class_name=ion%20channel

Metabolites that are annotated for annotated for both GPCR Class A and for one or more ion channels:

http://zinc15.docking.org/substances/subsets/metabolites/?genes-any-sub_class_name=GPCR-A&genes-any-major_class_name=ion%20channel

Compounds of biological origin have 3-ring systems:

http://zinc15.docking.org/substances/subsets/biogenic/having/rings/subsets/triple/

All individual species-specific targets for the MCHR2 gene:

http://zinc15.docking.org/genes/MCHR2/targets/

Compounds that are world drugs and natural products:

http://zinc15.docking.org/substances/subsets/world+natural-products/

Genes that have no compounds annotated for them at 1uM or better and are also for sale.

http://zinc15.docking.org/genes/having/no-activities/subsets/1uM/?related.purchasability=for-sale&num_substances-ge=1

Purchasable compounds for the APLNR gene in listing format:

http://zinc15.docking.org/genes/APLNR/substances/subsets/for-sale/table.html

Purchasable compounds for the delta opioid receptor OPRD1 in tile format:

http://zinc15.docking.org/genes/APLNR/substances/subsets/for-sale/

GPCR Class A genes with no compounds active at 100nM or better:

http://zinc15.docking.org/genes/subsets/gpcra/having/no-activities/subsets/100nM/?num_substances-ge=1

GPCR Class F genes with no compound active at 1uM or better:

http://zinc15.docking.org/genes/subsets/gpcrf/having/no-activities/subsets/1uM/

5HT ligands, colored by endogenous ligand

http://zinc15.docking.org/genes/HTR1D/substances/?highlight=5-HT&ecfp4_fp-tanimoto=NCCc1c%5BnH%5Dc2ccc%28O%29cc12

and sorted by affinity....

http://zinc15.docking.org/genes/HTR1D/activities/?highlight=5-HT&substance.ecfp4_fp-tanimoto=NCCc1c%5BnH%5Dc2ccc%28O%29cc12

Level 2 questions - edit URL by hand

This is usually because we have not yet gotten around to writing a graphical interface for this class of questions.

Description

zinc15.docking.org/substances.txt:smiles,zinc_id,tanimoto_similarity?catalog.purchasable%20gt%209&ecfp4.data%20similarto%20CC(=O)Oc1ccccc1C(=O)O%20within%20.5?count=all

How many primary amines are available for sale in preparative quantities?

URL="zinc15.docking.org:8015/substances.txt?substance.structure:contains=[ND1]&catalog.bb=True&substance.purchasability:gt=9&count=all"
wget -o log -O amines.smi "$URL"
wc -l amines.smi

answer: xxxx

Table 6

1 compounds:

http://zinc15.docking.org/substances.txt:smiles,zinc_id?structure-contains=CS(=O)(=O)[ND1]&substance.purchasability=for-sale

genes: 2

http://zinc15.docking.org/substances.txt:smiles,zinc_id?substance.purchasability=for-sale&structure-contains=C(=O)[ND2][OD1]

3

http://zinc15.docking.org/substances.txt:smiles,zinc_id?purchasability=for-sale&structure-contains=cC(=O)[OD1]

4

zinc15.docking.org/v1/substances.txt:smiles,zinc_id?purchasability=for-sale&structure-contains=CC(=O)[OD1]

5.

zinc15.docking.org/substances.txt:smiles,zinc_id?purchasability=for-sale&structure-contains=[SH]&count=all

6. Primary amines.

Table 7 - What genes do warheads hit?

compounds: 1

zinc15.docking.org/substances.txt:smiles,zinc_id?structure-contains=CS(=O)(=O)[ND1]&purchasability=for-sale

2

zinc15.docking.org/substances.txt:smiles,zinc_id?purchasability=for-sale&structure-contains=C(=O)[ND2][OD1]

3

zinc15.docking.org/substances.txt:smiles,zinc_id?purchasability=for-sale&structure-contains=cC(=O)

4

http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.purchasability%20gt%209&structure%20contains%20CC(=O)[OD1]

5.

http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.purchasability%20gt%209&structure%20contains%20[SH]

1.	http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20201,
2.	http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20202,
3.	http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20203,

&substance.purchasability >20 =20, =10, >1.

Level 3 questions - not possible in one line - requires python

Using a bit of python can dramatically extend the power of the ZINC website.

Examples mentioned in or implied by the 2015 paper

NEW TABLE 8

chemical warheads and the genes they hit as a function of affinity.

http://zincapi.ucsf.bkslab.org/v1/activities/txt:target.gene.name,substance.smiles,substance.zinc_id,substance.purchasability/activity.affinitynm ge 7&substance.structure%20contains%20cC(=O)[OD1]?count=all

Table 8B

http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20211,
http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20212,
http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20213,

&substance.purchasability >20 =20, =10, >1.

Figure 1

Drawn. probably to delete.

Figure 2

Non-purch final:

psql -h samekh -U test zinc15 -c "select count(distinct(n.sub_id_fk)) as num_compds, g.name as gene_name from gene g, annotation a, note n where g.gene_id = a.gene_fk and a.anno_id = n.anno_id_fk and n.affinitynm >= 5 and g.organism_fk = 1 group by g.name " > 1-10um.txt

Purch final:

psql -h samekh -U test zinc15 -c "select count(distinct(n.sub_id_fk)) as num_compds, g.name as gene_name from gene g, annotation a, note n, catalog_item ci, catalog c  where c.cat_id=ci.cat_id_fk and ci.sub_id_fk = n.sub_id_fk and g.gene_id = a.gene_fk and a.anno_id = n.anno_id_fk and n.affinitynm >= 5 and g.organism_fk = 2 and c.purchasable > 9  group by g.name" > 2-10um-purch.txt

Unknown

http://api.docking.org/v1/activities/txt:target.gene.name,sub_id_fk,affinitynm,substance.best_purchasbility

New non-purch

select count(distinct(n.sub_id_fk)) as num_compds, g.name as gene_name from gene g, annotation a, note n where g.gene_id = a.gene_fk and a.anno_id = n.anno_id_fk and n.affinitynm >= 6 and g.organism_fk = 1 group by g.name; (by organism x 4)

Purch:

select count(distinct(n.sub_id_fk)) as num_compds, g.name as gene_name from gene g, annotation a, note n, catalog_item ci, catalog c  where c.cat_id=ci.cat_id_fk and ci.sub_id_fk = n.sub_id_fk and g.gene_id = a.gene_fk and a.anno_id = n.anno_id_fk and n.affinitynm >= 8 and g.organism_fk = 2 and c.purchasable > 9  group by g.name  limit 10;

Actions

Translate

zinc15.docking.org/actions/translate

Nearest Metabolite

zinc15.docking.org/actions/translate

Build dockable library

zinc15.docking.org/actions/build-library

One-step reactions

zinc15.docking.org/actions/reaction

alter user zincfree set search_path = "$user", free, public;

Get supplier_codes for chembl20 compounds that match PAINS

wget -O- 'http://zinc15.docking.org/catalogs/chembl20/substances.json:zinc_id+catalog_items+patterns?patterns-any-origin_name=pains&count=all' | jq -r '[.zinc_id, (.patterns[] | select(.origin_name == "pains") | .name), (.catalog_items[] | select(.catalog_short_name == "chembl20") | .supplier_code)] | @csv' | csv --to-tsv | tee chembl-patterns.txt

gene-oriented

Compounds that are similar to dopamine and are endogenous human metabolites

http://zinc15.docking.org/substances/subsets/endogenous.txt:smiles+zinc_id+tanimoto_similarity?ecfp4_fp-tanimoto=c1cc(c(cc1CC[NH2])O)O

OR

http://zinc15.docking.org/substances/subsets/endogenous.txt:smiles+zinc_id+tanimoto_similarity?ecfp4_fp-tanimoto=33882

Similar to (drug) and has been in man

http://zinc15.docking.org/substances/subsets/in-man.txt:smiles+zinc_id+tanimoto_similarity?ecfp4_fp-tanimoto=c1cc2c(cc1O)C[C@H](CC2)N

http://zinc15.docking.org/genes

list of genes and their major classes

http://zinc15.docking.org/genes/txt:name%2Cdescription%2Ctarget_class.name%2Ctarget_class.major_target_class.name/

list of target classes

http://zinc15.docking.org/targetclasses.txt:name

list of major target classes

http://zinc15.docking.org/majorclasses.txt:name

enzyme genes

http://zinc15.docking.org/genes.txt:name%2Cdescription+target_class.name?majorclass.name=enzyme

http://zinc15.docking.org/targets.txt:gene.name+majorclass.name%20eq%20enzyme

what it does

.../substance.structure similarto c1ccccc1CCCOC within .7 using tanimoto

blah

/substance/txt:zinc_id/substance isa metabolite

asdfasdf

/substances/txt:zinc_id?sort=substance.structure+near+c1ccccc1CCNC+using+dice

The organism table (modified from ChEMBL)

http://zinc15.docking.org/organisms/txt:organism_id,code,description/

Table of Dopamine receptor genes

http://zinc15.docking.org/targets.txt:name,description,gene.description,uniprot,chembl,gene_fk,gene.name?gene.name-startswith=DRD

List of chemotype clusters (not too useful, but proof of concept)

http://zinc15.docking.org/clusters.txt:number+gene.name

All compound-target pairs with activity of 1nM or better

http://zinc15.docking.org/activities.txt:substance.zinc_id+substance.best_purchasability+substance.best_catalog+target.name+affinitynm?activity.affinitynm-gt=9

Search by inchikey prefix

translator:

http://zinc15.docking.org/apps/mol/convert?from=c1ccccc1&to=inchikey

blah

http://zinc15.docking.org/substances?references-any-pubmed_id=14695814

http://zinc15.docking.org/substances/?inchikey-startswith=LFQSCWFLJHTTHZ

Search by inchikey

http://zinc15.docking.org/substances/?inchikey=LFQSCWFLJHTTHZ-UHFFFAOYSA-N

Endogenous and Drug metabolites (ZINC, a new method to find problems in other databases)

http://zinc15.docking.org/catalogs/hmdbendo/substances/?catalogs-any-short_name=hmdbdrug

FDA approved but not in drugstore, generally this is due to stereochemistry issues in drugbank.

http://zinc15.docking.org/catalogs/dbfda/substances/?~catalogs-any-short_name=drugstore

first one: http://zinc15.docking.org/catalogs/lipid/substances/?~catalogs-any-short_name=hmdb

second one: (correct): http://zinc15.docking.org/catalogs/lipid/substances/?catalogs-any-short_name=lipid

blah

http://zinc15.docking.org/catalogs/foodb/substances/subsets/endogenous

Question: what compounds are in the "lipidomics" catalog but are NOT in HMDB (as we currently have it loaded):

http://zinc15.docking.org/catalogs/lipid/substances/?~catalogs-any-short_name=hmdb

thus, compounds sold by sigma aldrich that hit DRD2 and not HRH1 pace ChEMBL,10uM.

http://zinc15.docking.org/catalogs/sial/substances/?genes-any-name=DRD2&~genes-any-name=HRH1

Only one catalog, and it is sial:

http://zinc15.docking.org/catalogs/sial/substances/?~catalogs-any-short_name-ne=sial

We would like a variant for no other catalog of type 50,40,20,10 only. That's a request.

Metabolites that look like ethanol:

http://zinc15.docking.org/substances/subsets/metabolites/?ecfp4_fp-tanimoto-50=CCO

(produced in the gut by the bacterial flora)

Get fingerprint

http://zinc15.docking.org/substances/ZINC000018011573.txt:ecfp4_fp.as_base64

How many molecules are in pubchem?

http://zinc15.docking.org/catalogs/pubchem/substances?special=count

blah

http://zinc15.docking.org/catalogs/pubchem/substances?special=count-wait

blah

http://zinc15.docking.org/majorclasses/?substances-any-purchasability=for-sale 

blah

http://zinc15.docking.org/majorclasses/?substances-any-purchasability=not-for-sale

blah

http://zinc15.docking.org/majorclasses/?substances-memberof=biogenic

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