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?
How many ligands for ligand gated ion channels are for sale?
What is the nearest metabolite or drug to my compound?
thus for ZINC27, using 0.4 as cutoff
and for phenol aka c1ccccc1O, using Dice, 50 cutoff instead of Tanimoto (must be URL encoded, see dencoder
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:
Which genes have a ligand reported that binds at 10nM concentration or better?
Which targets do hydroxamic acids bind to?
Which vendors sell the most biogenic compounds (natural products), and what are those compounds?
How many primary amines as for sale in preparative quantitites?
World drugs with no gene target annotated and no SEA prediction
In-man compounds having no annotations in ChEMBL but DO have SEA predictions
World drugs having no annotations, 10uM or better
World drugs containing indole and having no genes annotated:
World drugs having one or more PAINS patterns:
Aggregators that have been in clinical trials:
Endogenous human metabolites that have PAINS patterns (lots of incorrectly curated, please tell the source databases)
Compounds of biological origin that are also FDA approved drugs:
Biogenic compounds that hit phosphatase targets
Biogenic compounds that hit a GPCR-A target and are predicted for one or more ion channels using SEA:
Metabolites that are annotated for annotated for both GPCR Class A and for one or more ion channels:
Compounds of biological origin have 3-ring systems:
All individual species-specific targets for the MCHR2 gene:
Compounds that are world drugs and natural products:
Genes that have no compounds annotated for them at 1uM or better and are also for sale.
Purchasable compounds for the APLNR gene in listing format:
Purchasable compounds for the delta opioid receptor OPRD1 in tile format:
GPCR Class A genes with no compounds active at 100nM or better:
GPCR Class F genes with no compound active at 1uM or better:
5HT ligands, colored by endogenous ligand
and sorted by affinity....
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.
At the moment (Oct 7, 2015) many constraints (after the ?) still need to be edited by hand. Another thing is the having clause, currently by hand, but soon, graphically.
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 "$URL" wc -l amines.smi
6. Primary amines.
Table 7 - What genes do warheads hit?
1. http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20201, 2. http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20202, 3. http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20203,
&substance.purchasability >20 =20, =10, >1.
Level 3 questions - not possible in one line - requires python
Using a bit of python can dramatically extend the power of the ZINC website.
NEW TABLE 8
chemical warheads and the genes they hit as a function of affinity.
http://zincapi.ucsf.bkslab.org/v1/activities/txt:target.gene.name,substance.smiles,substance.zinc_id,substance.purchasability/activity.affinitynm ge 7&substance.structure%20contains%20cC(=O)[OD1]?count=all
http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20211, http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20212, http://zincapi.ucsf.bkslab.org/v1/substances/txt:smiles,zinc_id/substance.features%20contains%20213,
&substance.purchasability >20 =20, =10, >1.
Build dockable library
alter user zincfree set search_path = "$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
Compounds that are similar to dopamine and are endogenous human metabolites
Similar to (drug) and has been in man
list of genes and their major classes
list of target classes
list of major target classes
what it does
.../substance.structure similarto c1ccccc1CCCOC within .7 using tanimoto
/substance/txt:zinc_id/substance isa metabolite
The organism table (modified from ChEMBL)
Table of Dopamine receptor genes
List of chemotype clusters (not too useful, but proof of concept)
All compound-target pairs with activity of 1nM or better
Search by inchikey
Endogenous and Drug metabolites (ZINC, a new method to find problems in other databases)
FDA approved but not in drugstore, generally this is due to stereochemistry issues in drugbank.
second one: (correct):
Question: what compounds are in the "lipidomics" catalog but are NOT in HMDB (as we currently have it loaded):
thus, compounds sold by sigma aldrich that hit DRD2 and not HRH1 pace ChEMBL,10uM.
Only one catalog, and it is 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:
(produced in the gut by the bacterial flora)
How many molecules are in pubchem?
Browse all substances in ZINC,
Browse available substance subsets
To ask for purchasable metabolites
Substance "home page", where you can search for molecules
Substance help page
Download substance in SMILES format (likewise for .sdf, .mol2, .json, .xml, .txt, .xls, .csv and .tsv formats.)
Download a table of data with smiles, zinc_id, mwt, logP, and rotatable bonds.
To get compounds that bind DRD2
To get compounds similar to Aspirin
http://zinc15.docking.org/substances?ecfp4_fp=53 (the ZINC ID for Aspirin)
To get compounds containing a primary basic amine
To get compounds similar to 2-chlorophenol
To get compounds reported to bind DRD2 and not HRH1 and are purchasable and are FDA approved drugs, and contain a primary amine:
We now take up the other resources in ZINC in turn.
All catalogs; The Sigma catalog; All items Enamine sells:
http://zinc15.docking.org/catalogs http://zinc15.docking.org/catalogs/sial http://zinc15.docking.org/catalogs/enamine/items
All FDA approved drugs
To get purchasable building blocks containing a nitrile (note # is not valid in URLs %23 is urlencoded #).
All genes, all gene subsets
Thymidine kinase, human only, compounds; compounds that have been in man and are available for immediate delivery
Serotonin 2A cell surface receptor (GPCR); only those in clinical trials; immediate delivery and current clinical trials.
http://zinc15.docking.org/genes/HTR2A/substances/ http://zinc15.docking.org/genes/HTR2A/substances/having/trials http://zinc15.docking.org/genes/HTR2A/substances/subsets/now/having/trials/subsets/current
Predicted ligands for SERT, strong predictions, strong and for sale
== Figure 1 ==
Drawn. probably to delete.
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
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
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)
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
natural products with names
Back to ZINC15:examples