ZINC15:examples

This continues to be an aspirational document, but we really are working on it!

Examples are organized by

• a) whether our solution is web accessible (public) or requires ssh access (private)

and

• level of difficulty - see ZINC15:Levels for difficulty levels

Please see also ZINC15:videos for discussions of various topics and ZINC15:examples:screening and ZINC15:examples:resources for more examples.

Public Access - can be answered using zinc15.docking.org

Level 1 questions - easy to answer 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 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.

Private access required

Level 4 - privileged access

Ask us if you require this level of access to ZINC.

Level 6 - SQL

How to calculate results from the ZINC15 2015 paper:

Table 2 - Genes, Uniprot codes and annotated compounds by affinity bin ==

• * select organism_fk, count(gene_id) from gene group by organism_fk;

zinc15.docking.org/genes.txt:count(*)?group-by=organism_fk

• + select g.organism_fk, count(a.anno_id) from annotation a, gene g where a.gene_fk = g.gene_id group by g.organism_fk;

zinc15.docking.org/targets.txt:count(*)?group-by=gene.organism_fk

• $ select count(distinct(n.sub_id_fk)),g.organism_fk 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 >= 9 group by g.organism_fk;

zinc15.docking.org/  not sure we can do this!

Table 3 - Gene Target Classes

• * select count(g.gene_id),tc.major_class from target_class tc, gene g where g.target_class_fk = tc.target_class_id group by tc.major_class order by tc.major_class

• + select count(distinct(s.sub_id)),tc.major_class from gene g, substance s, note n, annotation a, target_class tc where g.gene_id = a.gene_fk and g.target_class_fk = tc.target_class_id and n.anno_id_fk = a.anno_id and s.sub_id = n.sub_id_fk and s.purchasability >20, 20, 10 group by tc.major_class

• $ select count(distinct(g.gene_id)), tc.major_class from target_class tc, gene g, substance s, note n, annotation a where s.sub_id = n.sub_id_fk and a.anno_id = n.anno_id_fk and a.gene_fk = g.gene_id and g.target_class_fk = tc.target_class_id and s.purchasability > 9 group by tc.major_class;

Table 4 - Chemical Diversity by Gene

4) histogram of clusters per gene.

select c.gene_fk, g.name, count(c.cluster_id) from cluster c, gene g where g.gene_id = c.gene_fk and c.ordinal = 1 group by c.gene_fk,g.name order by count(c.cluster_id) desc;

for any one pick the smiles:

select smiles,sub_id from substance where sub_id in (select rep_sub_id_fk from cluster where gene_fk = 57387 and ordinal=1);

another

select c.gene_fk, g.name, count(c.cluster_id) from cluster c, gene g where g.gene_id = c.gene_fk and c.ordinal = 1 group by c.gene_fk,g.name order by count(c.cluster_id) desc;

another

select gene_fk, count(cluster_id) from cluster where ordinal = 1 group by gene_fk order by count(cluster_id) desc ;

Table 5 - Genes per compound as a function of affinity cutoff (polypharmacology) this is almost for sure wrong:

select sub_id  count(sub_id_fk) from note as n join annotation as a on n.anno_id_fk = a.anno_id join gene as g on g.gene_id = a.gene_fk group by n.sub_id_fk having min(n.affinitynM) >= 9;

NEW

Non purch:

select count(sub_id_fk) as num_compounds, cgi as having_num_genes from (select n.sub_id_fk as sub_id_fk , count(distinct(g.gene_id)) as cgi 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 >= 9 group by n.sub_id_fk) as t group by cgi order by cgi;

Heavy hitters:

select n.sub_id_fk as sub_id_fk , count(distinct(g.gene_id)) as cgi 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 >= 9 group by n.sub_id_fk order by cgi desc limit 10;

Purch:

select count(sub_id_fk) as num_compounds, cgi as having_num_genes from (select n.sub_id_fk as sub_id_fk , count(distinct(g.gene_id)) as cgi 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 c.purchasable>9 group by n.sub_id_fk) as t group by cgi order by cgi;

Heavy hitters (purch):

select n.sub_id_fk as sub_id_fk , count(distinct(g.gene_id)) as cgi 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 c.purchasable>9 group by n.sub_id_fk

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;