Bitter taste is one of the basic taste modalities. It is innately aversive for various species, and can be elicited by numerous,
chemically different compounds. The aim of this database is to gather information about bitter-tasting natural and synthetic compounds,
and their cognate bitter taste receptors (T2Rs or TAS2Rs).
Human
For Human (Homo sapiens), BitterDB contains information on 26 functional bitter taste receptors (TAS2Rs). Of these, 23 have experimentally validated ligands and the remaining 3 are orphans.
Mouse
For Mouse (Mus musculus), BitterDB contains information on 35 functional bitter taste receptors (TAS2Rs). Of these, 26 have experimentally validated ligands and the remaining 9 are orphans.
Chicken
For Chicken (Gallus gallus), BitterDB contains information on 3 functional bitter taste receptors TAS2Rs. All 3 receptors have experimentally validated ligands.
Cat
For Domestic Cat (Felis catus), BitterDB contains information on 12 functional bitter taste receptors (TAS2Rs). Of these, 8 have experimentally confirmed ligands and the remaining 4 are orphans.
Platypus
For Platypus (Ornithorhynchus anatinus), BitterDB contains information on 7 functional bitter taste receptors TAS2Rs. Of these, 5 have experimentally validated ligands and the remaining 2 are still orphaned.
Echidna
For Short-Beaked Echidna (Tachyglossus aculeatus), BitterDB contains information on 2 functional bitter taste receptors TAS2Rs. Of these, 2 have experimentally validated ligands and 1 remains an orphan.
Cattle
For Cattle (Bos taurus), BitterDB contains information on 1 functional bitter taste receptor TAS2Rs. For which there are 6 experimentally confirmed ligands.
Elephant
For African Elephant (Loxodonta africana) there is information about 1 functional bitter taste receptor TAS2Rs in BitterDB. There are 6 experimentally confirmed ligands.
Opossum
For Opossum (Monodelphis domestica), BitterDB contains information on 1 functional bitter taste receptor TAS2Rs. For which no experimentally confirmed ligands are available yet.
Quoll
For Eastern Quoll (Dasyurus viverrinus), BitterDB contains information about 1 functional bitter taste receptor TAS2Rs. For which there are 4 experimentally confirmed ligands.
Tasmanian Devil
For Tasmanian Devil (Sarcophilus harrisii), BitterDB contains information on 1 functional bitter taste receptor TAS2Rs. For which no experimentally validated ligands are available.
Wallaby
For Wallaby (Macropus eugenii), BitterDB contains information about 1 functional bitter taste receptor TAS2Rs. For which there are 4 experimentally confirmed ligands.
Koala
For Koala (Phascolarctos cinereus), BitterDB contains information on 1 functional bitter taste receptor TAS2Rs. There are 4 experimentally confirmed ligands.
Dog
For Dog (Canis familiaris), BitterDB contains information on 16 functional bitter taste receptors TAS2Rs. Of these, 9 have experimentally validated ligands and 7 are orphan.
Fish:
5 species were grouped together in Fish: Mexican Tetra (Astyanax mexicanus), West Indian Coelacanth (Latimeria chalumnae), Zebrafish (Danio rerio), European Carp (Cyprinus carpio) and Smalltooth Sawfish (Pristis pectinata). For Fish, BitterDB contains information on 19 functional TAS2R bitter taste receptors. Of these, 17 have experimentally validated ligands and 2 are currently orphaned.
Vampire Bat
For Vampiter Bat (Desmodus rotundus), BitterDB contains information on 8 functional bitter taste receptors TAS2Rs. Of these, 5 have experimentally validated ligands and 3 are orphan.
Frog
For American Bullfrog (Lithobates catesbeianus), BitterDB contains information on 11 functional bitter taste receptors (TAS2Rs). Of these, 5 have experimentally validated ligands and 6 are currently orphaned.
Shark
4 species have been grouped together in Shark: Small-Spotted Catshark (Scyliorhinus canicula), Cloudy Catshark (Scyliorhinus torazame), Brown-banded Bamboo Shark (Chiloscyllium punctatum) and White-Spotted Bamboo Shark (Chiloscyllium plagiosum). For Shark, information on 4 functional bitter taste receptor TAS2Rs is available in BitterDB. Experimentally validated ligands are available for all of them.
Stingray
For Red Stingray (Hemitrygon akajei), BitterDB contains information on 1 functional bitter taste receptor TAS2Rs. There are 3 experimentally confirmed ligands.
Bird
4 species have been grouped together in Bird: Zebra Finch (Taeniopygia guttata), Anna's Hummingbird (Calypte anna), Chimney Swift (Chaetura pelagica) and Chuck-Will's Widow (Antrostomus carolinensis). For Bird, BitterDB contains information on 13 functional bitter taste receptor TAS2Rs. Experimentally validated ligands are available for all.
Turkey
For Wild Turkey (Meleagris gallopavo), BitterDB contains information on 2 functional bitter taste receptors TAS2Rs. Experimentally validated ligands are available for all.
Primate
34 species have been grouped together in Primate: Common Chimpanzee (Pan troglodytes), Northern White-Cheeked Gibbon (Nomascus leucogenys), Rhesus Macaque (Macaca mulatta), White-Headed Langur (Trachypithecus leucocephalus), Red-Shanked Douc (Pygathrix nemaeus), Common Marmoset (Callithrix jacchus), Cotton-Top Tamarin (Saguinus oedipus), Coppery Titi Monkey (Plecturocebus cupreus), White-Faced Saki (Pithecia pithecia), Bald Uakari (Cacajao calvus), White-Nosed Saki (Chiropotes albinasus), Northern Greater Galago (Otolemur garnettii), Ring-Tailed Lemur (Lemur catta), Black Lemur (Eulemur macaco), Black-and-White Ruffed Lemur (Varecia variegata), Greater Bamboo Lemur (Prolemur simus), Golden Bamboo Lemur (Hapalemur aureus), Eastern Lesser Bamboo Lemur (Hapalemur griseus), Japanese Macaque (Macaca fuscata), Long-Nosed Monkey (Nasalis larvatus), East Javan Langur (Trachypithecus auratus), Raffles Banded Langur (Presbytis femoralis), Mantled Guereza (Colobus guereza), Angola Colobus (Colobus angolensis), Heck's Macaque (Macaca hecki), Celebes Crested Macaque (Macaca nigra), Gorontalo Macaque (Macaca nigrescens), Tonkean Macaque (Macaca tonkeana), Common Marmoset (Callithrix jacchus), Azara's Night Monkey (Aotus azarae), Colombian White-Faced Capuchin (Cebus capucinus), Geoffroy's Spider Monkey (Ateles geoffroyi), Mantled Howler (Alouatta Palliata) and Silvery Lutung (Trachypithecus cristatus). For Primate, BitterDB contains information on 63 functional bitter taste receptor TAS2Rs. Experimentally validated ligands are available for all of them. Of these, 24 have experimentally validated ligands and 39 are orphan.
Blind Mole Rat
For the Blind Mole Rat (Spalax galili), BitterDB contains information on 6 functional bitter taste receptors TAS2Rs. Of these, 3 have experimentally validated ligands and 3 remain orphaned for the time being.
How to Cite BitterDB:
Evgenii Ziaikin, Moran David, Sofya Uspenskaya, Masha Niv, BitterDB: 2024 update on bitter ligands and taste receptors, Nucleic Acids Research, 2024, doi: 10.1093/nar/gkae1044 Click here to view the paper:BitterDB 2024 paper
Ayana Dagan-Wiener, Antonella Di Pizio, Ido Nissim, Malkeet S. Bahia, Nitzan Dubovski, Eitan Margulis, Masha Y. Niv, BitterDB: taste ligands and receptors database in 2019, Nucleic Acids Research, 2019, 47(D1), D1179–D1185 Click here to view the paper:BitterDB 2019 paper
Ayana Wiener, Marina Shudler, Anat Levit, Masha Y. Niv, BitterDB: a database of bitter compounds, 2012, Nucleic Acids Research, 40(D1), D413–D419 Click here to view the paper:BitterDB paper
BitterDB underwent a major update in 2024:
BitterDB now holds over 2400 bitter molecules. For ~800 molecules, at least one associated bitter taste receptor (TAS2R) is reported. The overall number of ligand-TAS2R associations is now ~2000. BitterDB is extended to 66 additional species (including dog, birds, fishes and primates) and links to available experimental structures and AlphaFold models of TAS2Rs are provided.
BitterDB provides several ways to investigate the bitter world: search for bitter compounds by
different criteria, search for bitter molecules with structure similar to a query compound,
Browse bitter receptors and more.
BitterPredict is a machine learning classifier that predicts whether a chemical compound will taste bitter or not based on its chemical structure
Click here to view the paper:BitterPredict paper
How to Cite BitterPredict: Ayana Dagan-Wiener, Ido Nissim, Natalie Ben Abu, Gigliola Borgonovo, Angela Bassoli, Masha Y. Niv, Bitter or not? BitterPredict, a tool for predicting taste from chemical structure, Scientific Reports, 2017, 7, 12074
BitterIntense is a machine learning tool developed to classify molecules as either "very bitter" or "not very bitter" based on their chemical structure
Click here to view the paper:BitterIntense paper
How to Cite BitterIntense: Eitan Margulis, Ayana Dagan-Wiener, Robert S. Ives, Sara Jaffari, Karsten Siems, Masha Y. Niv, Intense bitterness of molecules: Machine learning for expediting drug discovery, Computational and Structural Biotechnology Journal, 2021, 19, 568-576
BitterMatch is a machine learning algorithm designed to predict associations between ligands and bitter taste receptors (TAS2Rs)
Click here to view the paper:BitterMatch paper
How to Cite BitterMatch: Eitan Margulis, Yuli Slavutsky, Tatjana Lang, Maik Behrens, Yuval Benjamini, Masha Y. Niv, BitterMatch: recommendation systems for matching molecules with bitter taste receptors, 2022, Journal of Cheminformatics, 14(45)
BitterMasS is a machine learning tool for predicting the bitterness of a compound based on its mass spectrum
Click here to view the paper:BitterMasS paper
How to Cite BitterMasS: Evgenii Ziaikin, Edisson Tello, Devin G. Peterson, Masha Y. Niv, BitterMasS: Predicting Bitterness from Mass Spectra, Journal of Agricultural and Food Chemistry, 2024, 72(18), 10537–10547
If you would like to receive information about new uploads to the database,
please send as mail to: nivlab@agri.huji.ac.il
Ayana Dagan Wiener, Ido Nissim, Natalie Ben Abu, Gigliola Borgonovo, Angela Bassoli, Masha Y. Niv. Bitter or not? BitterPredict, a tool for predicting taste from chemical structure.
Scientific Reports 7, 12074, doi:10.1038/s41598-017-12359-7 (2017)
For more details please contact us: nivlab@agri.huji.ac.il
Bitterness and Toxicity
Ido Nissim, Ayana Dagan Wiener, Masha Y. Niv. The taste of toxicity: a quantitative analysis of bitter and toxic molecules.
IUBMB Life, doi: 10.1002/iub.1694 (2017)
BitterIntense is a machine learning tool developed to classify molecules as either "very bitter" or "not very bitter" based on their chemical structure.
Eitan Margulis, Ayana Dagan-Wiener, Robert S. Ives, Sara Jaffari, Karsten Siems, Masha Y. Niv, Intense bitterness of molecules: Machine learning for expediting drug discovery, Computational and Structural Biotechnology Journal, 2021, 19, 568-576
For more details please contact us: nivlab@agri.huji.ac.il
BitterMatch
BitterMatch is a machine learning algorithm designed to predict associations between ligands and bitter taste receptors (TAS2Rs).
Eitan Margulis, Yuli Slavutsky, Tatjana Lang, Maik Behrens, Yuval Benjamini, Masha Y. Niv, BitterMatch: recommendation systems for matching molecules with bitter taste receptors, 2022, Journal of Cheminformatics, 14(45)
Ayana Dagan Wiener, Ido Nissim, Natalie Ben Abu, Gigliola Borgonovo, Angela Bassoli, Masha Y. Niv. Bitter or not? BitterPredict, a tool for predicting taste from chemical structure.
Scientific Reports 7, 12074, doi:10.1038/s41598-017-12359-7 (2017)
The Alignment contains the 26 human bitter taste receptors, it is displayed with MSAViewer [1]. All alignments were generated using the T-Coffee [2] on the EMBL-EBI webserver [3].
Human Bitter Receptors Cross-Species Alignments
Alignments of each human TAS2R with similar validated bitter taste receptors from different species. All receptors in the alignment are documented in BitterDB and share over 50% identity similarity with the selected human receptor, offering insights into cross-species functional and evolutionary relationships.
When using this Alignment, please cite us: Evgenii Ziaikin, Moran David, Sofya Uspenskaya, Masha Niv, BitterDB: 2024 update on bitter ligands and taste receptors, Nucleic Acids Research, 2024, doi: 10.1093/nar/gkae1044
References:
Yachdav G. et al. MSAViewer: interactive JavaScript visualization of multiple sequence alignments, Bioinformatics, 2016, 32(22), 3501–3503
Notredame C. et al. T-coffee: a novel method for fast and accurate multiple sequence alignment, Journal of Molecular Biology, 2000, 302(1), 205-217
Madeira F. et al. The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024, Nucleic Acids Research, 2024, 52(W1), W521–W525
Contact us
To contact us please send email to nivlab@agri.huji.ac.il
Any suggestions and comments will be highly appreciated!
Reference for citation:
Dagan-Wiener, Ayana ; Di Pizio, Antonella; Nissim, Ido; Singh Bahia, Malkeet ; dubovski, nitzan; margulis, eitan; Niv, Masha. BitterDB: Taste ligands and receptors database in 2019. Nucleic Acids Res 2019,gky974
Click here to view the paper:BitterDB paper
Ayana Wiener; Marina Shudler; Anat Levit; Masha Y. Niv. BitterDB: a database of bitter compounds. Nucleic Acids Res 2012, 40(Database issue):D413-419
Click here to view the paper:BitterDB paper
Evgenii Ziaikin, Moran David, Sofya Uspenskaya, Masha Niv, BitterDB: 2024 update on bitter ligands and taste receptors, Nucleic Acids Research, 2024, doi: 10.1093/nar/gkae1044
BitterDB new paper
Ayana Dagan-Wiener, Antonella Di Pizio, Ido Nissim, Malkeet S. Bahia, Nitzan Dubovski, Eitan Margulis, Masha Y. Niv, BitterDB: taste ligands and receptors database in 2019, Nucleic Acids Research, 2019, 47(D1), D1179–D1185
BitterDB 2019 paper
Ayana Wiener, Marina Shudler, Anat Levit, Masha Y. Niv, BitterDB: a database of bitter compounds, 2012, Nucleic Acids Research, 40(D1), D413–D419
BitterDB 2012 paper
We are interested in extending the BitterDB database.
If you are aware of any bitter compounds that are not included in this database,
please upload them below or send them via email to:
nivlab@agri.huji.ac.il
Please note that fields with * are required.
The BitterDB contains information to maximize the utility of the resource.
To get help for specific part just click the icon which appear next to it.
Clicking it will open a popup window with the help.
All the help for this site is also available on this page.
How to cite BitterDB: Evgenii Ziaikin, Moran David, Sofya Uspenskaya, Masha Niv, BitterDB: 2024 update on bitter ligands and taste receptors, Nucleic Acids Research, 2024, doi: 10.1093/nar/gkae1044 Click here to view the paper:BitterDB paper
To Search BitterDB Compounds enter your query in the search box and click search.
You can enter compound name, SMILES, CAS number, Formula, IUPAC Name and properties.
For search by specific criteria please go to advanced search.
The simple search is implemented as what is sometimes referred to as "implied Boolean logic", meaning that
certain characters have special meaning at the beginning or end of words, such as.
+ stands for AND
- stands for NOT
[no operator] implies OR
The asterisk serves as the truncation (or wildcard) operator. It should be appended to the word to be affected. Words match if they begin with the word preceding the * operator.
This search form contains a number of fields, all of which are optional
(although at least one field is needed to perform a search).
The entered search terms 'ANDed' together, meaning that the compounds
that are found comply with ALL the terms that were specified.
The BitterDB allows searching compounds by the following physical properties that were computed by RDKit (Open-source cheminformatics; http://www.rdkit.org) for each compound:
Log of the octanol-water partition coefficient using Crippen's approch.[1]
Hydrogen Bond Acceptors are defined as heteroatoms (Oxygen, Nitrogen, Sulfur, or Phosphorus) with one or more lone pairs, excluding atoms with positive formal charges, amide and pyrrole-type Nitrogens, and aromatic Oxygen and Sulfur atoms in heterocyclic rings.
Hydrogen Bond Donors are defined as heteroatoms (Oxygen, Nitrogen, Sulfur, or Phosphorus) with one or more attached Hydrogen atoms.
The property indicates if the compound is natural or synthetic. This property (where available) was obtained from the literature.
The extracted from the Acute Oral Toxicity
Database [2] were added when available, as estimates for compounds� toxicity. LD50 Values in BitterDB are ranging from >0 to 5000.
S. A. Wildman and G. M. Crippen *JCICS* _39_ 868-873 (1999)
Tomasulo, P. (2002) ChemIDplus-super source for chemical and drug information. Medical
reference services quarterly, 21, 53-59.
The BitterDB allows searching bitter compounds using different textual keywords. BitterDB can be searched by:
- Simplified Molecular Input Line Entry Specification is a specification for unambiguously describing the structure of chemical molecules using short ASCII strings
The BitterDB allows searching compounds by their associated receptors.
Checking more than one box is equivalent for asking for ligands of at least one of the receptors that were checked.
The disable receptors options are receptors that are still orphan (i.e receptors with no known ligands).
Structure Similarity Search
2D Structure Similarity Search allows to locate records that are similar to a chemical structure query.
you can draw a molecule or you can insert a valid SMILES
string in the upper box.
Similarity is measured by the Tanimoto equation and the fingerprint.
This fingerprint consists of series of chemical substructure "keys".
Each key denotes the presence or absence of a particular substructure in a molecule. The fingerprint does not consider variation in stereochemical or isotopic information.
Collectively, these binary keys provide a "fingerprint" of a particular chemical structure valence-bond form.
We used openBabel [1] for calculating MACCS fingerprints and for the similarity search.
References
Rajarshi Guha, Michael T. Howard, Geoffrey R. Hutchison, Peter Murray-Rust, Henry Rzepa, Christoph Steinbeck, Joerg Kurt Wegner, Egon Willighagen. "The Blue Obelisk -- Interoperability in Chemical Informatics." J. Chem. Inf. Model. (2006) 46(3) 991-998.
The Results to your search are sort by their bitterDB id.
In order to get a full compound entry click on the compound id or it's name.
It is possible also to download a SDF file of selected compound, check the
required compounds and click on the download button in the top right of the page. The Download all button downloads all search results.
Receptor Search
To search BitterDB Receptors enter the query terms in the search box and click search.
The BitterDB allows searching bitter receptors using different criteria:
Receptor Name:
Search bitter Receptors by its Gene name, Protein Name or other common name the receptor is associated with.
For example, Taste receptor type 2 member 38 can be searched by the following keywords:
hTAS2R38, TAS2R38, T2R38,T2R61, TAS2R61, hTAS2R61, Taste receptor type 2 member 61, PTC, PTC bitter taste receptor.
This search option is implemented via the "implied Boolean logic".
Ligand Name:
Search bitter receptors by their associated ligand.
For example, the results of the search term "caffeine" are five different bitter receptors.
The search option is implemented via the implied Boolean logic".
Search bitter Receptors which have/have not mutation data.
Has Ligands:
Search bitter Receptors which have known ligands or those that are orphan receptors.
If these fields are used with a term in the top search box they are 'ANDed' together, meaning that the receptors that are found comply with ALL the terms that were specified.
The asterisk serves as the truncation (or wildcard) operator.
It should be appended to the word to be affected.
Words match if they begin with the word preceding the * operator.
The user may use the 'Browse BitterDB Compounds' option to browse through a table
with all BitterDB compounds and their properties. The compounds can be sorted by
different criteria: BitterDB ID, number of associated receptors, molecular weight, logP and more,
by clicking the arrows in the columns names. The search box on the top right hand side of the table enables
searching for specific compounds in the compound table. The search option is implemented such,
that it filters the relevant results as soon as the search term is typed. Clicking on a specific compound name opens the compound entry page.
Browse BitterDB receptors
The user may use the 'Browse BitterDB Receptors' option to browse through a table of the 75 bitter
taste receptors including 25,35,3,12 receptors from human,mouse,chicken,cat respectively. For each receptor, its alternative names,
the number of bitter ligands that it is known to bind and availability of mutational data, are indicated.
The receptors can be sorted according to different criteria: BitterDB receptor ID, number of associated bitter ligands,
receptor name and more, by clicking the arrows in the columns names. The search box on the top right hand side of the
table enables searching for specific receptors. The search option is implemented such that it filters the relevant
results as soon as the search term is typed. Clicking on a specific receptor name opens the receptor entry page.
BitterPredict
BitterPredict is a classifier we developed recently, which predicts whether a compound is bitter or not, based on its chemical structure.
BitterPredict features and more details would be upon publication.
Human Bitter taste Receptors Alignment
The Alignment contains the 25 human bitter taste receptors, it is displayed with bioJS MSA[1]. The alignment was generated by Anat Levit using the PROMALS3D webserver[2]. It was generated with 11 sequence-distinct family A GPCRs, for which a crystal structure has been solved.
Pei, J., B.H. Kim, and N.V. Grishin.(2008)
PROMALS3D: a tool for multiple protein sequence and structure alignments.
Nucleic Acids Res 36(7): p. 2295-300. PubMedID: 18287115
Receptors can be searched using Receptor Name, Ligand Name or UniProtKB accession number. The Has mutation field allows you to search for receptors with or without mutation data and Has Ligands allows you to search for receptors with known ligands or orphan receptors. More detailed information can be found in the Help section.