• A Dating Site For Chemists and Biologists


    Probably everyone who reads the ChEMBL-og will have world-changing ideas - but it's really difficult to find someone to screen a few compounds for you - of course there are CROs who will want to meet, then prepare a quote for you, set up a CDA, receive payment, etc., but cash is difficult to get hold of, and the process will be slow. There are no grant mechanisms for this sort of thing either - imagine - "I'd like funds to test four compounds as potential inhibitors of snoraze" - no chance (at least with the panels I've sat on) too small, too speculative.... The bigger problem though is finding someone with the assay or the compounds.

    But, there's a lot of people with compounds to test, and a lot of biologists with assays that are easy to run in their labs, and they have expertise in, but who can't assemble sets of interesting compounds to profile. Why not just use the paradigm of a dating site to matchmake mutually compatible biologists and chemists - if there is a spark, it could develop into a long lasting (collaborative) relationship!

    Imagine something like:

    Biologist with HMGCoA reductase assay and expertise in cholesterol homeostasis would like to meet chemist with non-statin compounds likely to be brain penetrant to test a cool idea.

    Anyway, there's a toy FaceBook group that I've set up - just to get the idea across. I've pitched this as a national thing (so for me that means to the UK, for you somewhere different maybe) - not least that it's a lot easier to ship compounds around within a country than between - and also there's a clear match to downstream funding opportunities. I chose FaceBook, since most of the open LinkedIn groups I'm involved in are train-wrecks of spam and flame-wars.

    I think this idea is worth trying, or at least getting some discussion started over - huge thanks to Tom Heightman for our recent discussion on things that needed to be done in Chemical Biology in the UK.

    Maybe Google+ is another alternative.

  • Pfam domain searching of targets in ChEMBL


    One thing new in the backend and interface for this release of ChEMBL is the ability to search for targets containing particular PFAM domains. So if you know a PFAM id, you can search in the search box (and then select "Targets" for that domain. For example, PF00001 is the Pfam ID for the rhodopsin-like GPCRs.

    A couple of important things on this though - the current functionality does exactly what it says - it returns proteins that contain that domain - the compounds do not necessarily (and often in fact do not) bind at that domain. This multidomain, and multi protein target issue is a surprisingly big challenge, and is a big trap for the unwary. So caveat emptor.

    We do plan in the next release or two, provide a prediction of the likely/known compound binding domain (however here, for proteins that contain multiple copies of the predicted/lknown binding domain it is complicated....).

  • ChEMBL 13 Released

    We are pleased to announce the release of ChEMBL_13. This latest version of the ChEMBL database contains:
    • 1,296,266 compound records
    • 1,143,682 distinct compounds
    • 617,681 assays
    • 6,933,068 bioactivities
    • 8,845 targets
    • 44,682 documents
    • 8 data sources
    This release includes updates to the manually extracted Medicinal Chemistry literature, updates to OrangeBook drug approvals and a update from PubChem BioAssay. This release also contains data sets related to screening against human African Trypanosomiasis and Chagas disease. Both data sets have been deposited by the Drugs for Neglected Diseases Initiative (DNDi). For more details, please see ChEMBL-NTD website.

    Please refer to the ChEMBL_13 release notes for a more detailed description of all changes included in this release.

    We have also made a couple of minor updates to the interface which include
    • New Ligand Efficiency widget, which is displayed on the Target report card pages (e.g. CHEMBL331)

    You can download the data from the ChEMBL ftpsite: ftp://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/latest/

  • PPI-Net - UK National Network for Collaboration on Protein-Protein Interactions



    Yesterday I took part in a workshop on targeted libraries at the Univeristy of Leeds - it was a great meeting, with lots of good ideas on directing compound design towards this class of interaction (Protein-Protein Interactions, PPIs - now form a significant fraction of the interesting target systems for drug discovery and basic biology and the development of tool compounds/leads that modulate these is a major challenge due to the low ligand efficiency characteristics of the majority of PPI binding sites).

    There is a great website, with a collection of key references, contacts, etc.

    I came away determined to do a couple of things:

    1. Resurrect some old F77 code (yay!) to look at peptide binding pharmacophores.
    2. Try and play a bit with Facebook/LinkedIn as a sort of dating site for unattached chemical/biologists.

  • ACS meeting in San Diego


    Three of the group (Patricia Bento, Jon Chambers and I) are out at the ACS National in San Diego at the end of March. If you want to meet up and have a coffee, get in touch, if you'd like a talk on ChEMBL, I'm sure we could fit something in.

  • Paper: Toxicogenomics Investigation Under the eTOX Project

    A paper on some of the toxicogenomics work we are involved in under the IMI eTox project. The paper is Open Access :) and downloadable here.

    %T Toxicogenomics Investigation Under the eTOX Project
%A O. Taboureau
%A A. Hersey 
%A K. Audouze
%A L. Gautier 
%A U.P. Jacobsen
%A R. Akhtar 
%A F. Atkinson 
%A J.P. Overington
%A S. Brunak
%O http://dx.doi.org/10.4172/2153-0645.S7-001
%J Pharmacogenomics & Pharmacoproteomics
%V S7
%D 2012

  • Sequence-Structure alignment of the 11 structurally characterised distinct GPCRs

    Here is a joy formatted alignment of the (now) 11 sequence distinct rhodopsin-like GPCR structures - I've selected a representative for those for which there are multiple structures known - usually those that are most complete in terms of lack of disordered loops, etc. The alignment is quite unstable in parts, and several regions are open to interpretation.....

    The structures are:

    1. 3uon - human muscarinic M2 receptor
    2. 4daj - rat muscarinic M3 receptor
    3. 3rze - human histamine H1 receptor
    4. 2rh1 - human beta-2 adrenergic receptor
    5. 2vt4 - turkey beta-1 adrenergic receptor
    6. 3pbl - human dopamine D3 receptor
    7. 2ydv - human adenosine A2a receptor
    8. 3v2w - human sphingosine-1-phosphate receptor
    9. 3odu - human CCR4 receptor
    10. 2i35 - bovine rhodopsin
    11. 2z73 - squid rhodopsin
    The next to be released structures will almost certainly be the mu-opioid receptor (PDB code 4DKL) and the kappa-opioid receptor (PDB code 4DJH), which are on hold awaiting publication.


                               10        20        30        40        50  
3uon   (  20 )                                             tfevvfivl
4dajA  (  64 )                                             iwqvvfiaf
3rze   (  28 )                                                 mplvv
2rh1   (  29 )                                            devwvvgmgi
2vt4A  (  40 )                                               weagmsl
3pblA  (  32 )                                                   yal
2ydv   (   3 )                                             imgssvYit
3v2w   (  17 )           sdyvnydIIvrHYnyTgklnisa                ltsv
3oduA  (  27 )            pçfre-------------------------enanfnkiflpt
1u19A  (   1 )            mnGtegpnfyVPfsnktgvVrsPFeapQyyLaepwqFsmlAa
2z73A  (   9 )         etwwyNpsIvVhpHWref--------------dqvpdavYyslGi
                                                               aaaaa

                           60        70        80        90        100 
3uon   (  29 )    vagslSlvTiigNilVmvSIkvnrhLqtvnnyflfSLAcADliiGvfSMn
4dajA  (  73 )    ltgflAlvTiigNilVivAFkvnkqLktvnnyFllSLAcADliIGviSMn
3rze   (  33 )    vlsticlvTvglNllVlyAvrserkLhtvGnlYIvsLSvADliVGavVMp
2rh1   (  39 )    vmslivlaIvfgNvlVitAIakferLqtvtnyFItsLAcADlvMGlaVVp
2vt4A  (  47 )    lmalVvllIvagNvlViaAigstqrLqtltnlFItsLAcADlvvGllVVp
3pblA  (  35 )    sYcalilaIvfgNglVcmAVlkeraLqtttnyLVvsLAvADllvAtlVMp
2ydv   (  12 )    vElaiavlAilgNvlVcwAvwlnsnLqnvtnyFVvsAAaADilVGvlAIp
3v2w   (  51 )    vfiliCcfIileNifvlltiwktkkFhrpMYyFIgnLAlSDllaGvaYta
3oduA  (  44 )    iYsiIfltGivgNglvilvMgyqkklrsmtdkYRlhLSvADllFVitLpf
1u19A  (  43 )    yMflLimlGfpiNflTlyVTvqHkkLrtplNyILlnLAvADlfMVfg-GF
2z73A  (  40 )    fIgiCgiiGcggNgiViyLFtktksLqtpanmFiinLAfSDftFSlvNGf
                  aaaaaaaaaaaaaaaaaaaaaa      aaaaaaaaaaaaaaaaaa aaa

                           110       120       130       140       150 
3uon   (  79 )    lytlytvi-gyWplgpvvÇdlWlalDYvVSNAsVmNLliiSfdryfcvtk
4dajA  ( 123 )    lFttyiim-nrWalgnlaÇdlwLSiDYvASNAsVmNLlvISfDryfsitr
3rze   (  83 )    mnilyllm-skwsLgrplÇlfWLSmDYVASTASIfSVfiLCiDryrsvqq
2rh1   (  89 )    fgaahilm-kmWtfgnfwçefWTSiDVlCVTASIeTLcvIAvdryfAIts
2vt4A  (  97 )    fgatlvvr-gtWlwgsflçelWTSlDVlCVTAsIeTLcvIAiDrylaits
3pblA  (  85 )    wvvylevtggvWnfsricÇdvFVTlDVmMcTAsIwNLCaISidRytAVvm
2ydv   (  62 )    faiaIst---GfçaaçhgÇLfiACfVLVLTASSIfSLlaIAiDryiairi
3v2w   ( 101 )    Nlllsga--tTykLtPaqWFlREGsMFvALSASVfSLlaIAieryitmlk
3oduA  (  94 )    WavDAva---nWyfgnflÇkaVHviYTVNlYSSVwILAfISlDRylAiVh
1u19A  (  92 )    tTTlyTSlhGyFvfgptGÇnlEGffATLGGEIaLWSLvvLaieRyvvVck
2z73A  (  90 )    plMtiSCflkkWifgfaaÇkvYGfiGGiFGFMsIMTMAMiSiDrynViGr
                  aaaaaaa        aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa  

                           160       170       180       190       200 
3uon   ( 128 )    pltypvk---rttkmAgmmiaaAwvlSfilwapaIlfwqfivg-------
4dajA  ( 172 )    pltyrak---rttkrAgvmiglAwviSfvlWApaIlfwqyfvg-------
3rze   ( 132 )    plrylky---rtktrAsatilgawflSfl-WvipIlgwnh          
2rh1   ( 138 )    pfkyqSl---ltknkArviilmvwivSgltSflpIqmhwyr-----athq
2vt4A  ( 146 )    pfryqsl---mtrarAkviictvwaiSalvSflpImmhwWr-----dedp
3pblA  ( 135 )    pvhyqhgtgqsscrrValmitavwvlAfaVSc-pLlfgfNtTg-------
2ydv   ( 109 )    plryngl---vtgtrAkgiiaicwvlSfaIGltPmlgwnnÇgqp--kegk
3v2w   ( 156 )               nnfrlfllisacwviSlilGglPimgwn-----------
3oduA  ( 141 )    atn----sqrprkllAekvVyvgVwipAlllT-ipDfif-Anvsead---
1u19A  ( 142 )    pmsn----frfgenhaimgvafTwvmAlaCAapPlvgwSrYIPE------
2z73A  ( 140 )    pmaas---kkMshrrAfimiifVwlwSvlwAigPifgwGaYtLE------
                              aaaaaaaaaaaaaaaaaaa                   

                           210       220       230       240       250 
3uon   ( 168 )    ----vrtVedgeÇyIqff------snaavtfgtAiaaFylpviiMtvlyw
4dajA  ( 212 )    ----krtVppgeÇfIqfl------septitfgtAiaaFymPvtiMtilyw
3rze   ( 175 )           rredkÇeTdfy------dvtwfkvmtaiinFylPtllMlwfya
2rh1   ( 180 )    eAinÇyae-etçÇdff--------TnqayaiasSivSFyvplviMvfvYs
2vt4A  ( 188 )    qAlkçyqd-pgçÇdfv--------TnrayaiasSiiSFyipLliMifval
3pblA  ( 177 )    --------dptvÇsIs---------npdFViySSvvSFylPfgvTvlvya
2ydv   ( 154 )    ahsqgÇgegqvAÇlFedVV-----pmnYMVyfNffaCVlvPlllMlgvyl
3v2w   ( 184 )    ----ÇisalssÇSTVLP-------LYhkhYIlfCTtvFtllllsIvilYc
3oduA  ( 182 )    --------dryiÇdrfyp---ndlwvvvfqfqhimvglilPgivIlsCyc
1u19A  ( 182 )    -------GMQCSÇGIDYYTpheetnNesFViyMfvvHfiiPlivIffcyg
2z73A  ( 181 )    -------GVLCNÇSFdYIsr--dsttrsNIlcMFilGffgPiliiffCyf
                                            aaaaaaaaaaa aaaaaaaaaaaa

                           260       270       280       290       300 
3uon   ( 208 )    hisrasksri                   pppsrekkvtrtilaIllaFi
4dajA  ( 252 )    rIyketek                       like   aqTlsaIllaFi
3rze   ( 212 )    kIykaVrqhc                   lhmnrerkaakQLgfIMaaFi
2rh1   ( 221 )    rVfqeakrql                   kfclkeHkaLktlgiIMgtFt
2vt4A  ( 229 )    rvyreakeq                       irehkalktlgiImgvFt
3pblA  ( 210 )    rIyvvlkqrrrk-----------------gvplrekkatqMVaiVlgaFi
2ydv   ( 199 )    rIflaarrqlkqmesq             stlqkevhaakSLaiIvglFa
3v2w   ( 223 )    riyslvrtr                   asrssenvaLlkTViiVLsvFi
3oduA  ( 221 )    iIisklshs                     kghqkrkalktTviLilaFf
1u19A  ( 225 )    qLvftvkeaaaq------------qqesattqkaekevTrMviiMviaFl
2z73A  ( 222 )    nIvmsvsnhekemaamakrlnakelrkaqaganaemrlAkIsivIVsqFl
                  aaaaa                            aaaaaaaaaaaaaaaaa

                           310       320       330       340       350 
3uon   ( 398 )    itWapYNvmVlintfçap--------ç--ipntvwtiGywlCYinstiNp
4dajA  ( 501 )    itWtpyNimVlvntfçds--------ç--ipktywnlgywlCYiNStvNP
3rze   ( 426 )    lCWipYFiffmviafçkn--------ç--cnehlhmftiWlGYiNStlNP
2rh1   ( 284 )    lcWlpFFiVNivhviqdn----------lirkevyillNwiGYvNSgfNp
2vt4A  ( 301 )    lCWlpFFlvnivnvfnrd----------lvpdwlfvafnwlGYAnSAmnp
3pblA  ( 340 )    vCWlpFFltHvlnthçqt--------ç-hvspelysattwlGYvNsalNP
2ydv   ( 244 )    lCWlpLHiiNcftffçpd--------çshaplwlMylAivlSHtNSvvNP
3v2w   ( 267 )    acwapLFiLLllDvgçkvk------tç--diLfrAeyfLvlAvlNSgtNP
3oduA  ( 250 )    acWlpyyigisidsfilleiikqgçefentvhkwisitEAlAFfHCclNp
1u19A  ( 263 )    iCWlpYAgvAfyIfthqgsd---------fgpifMTipAFfAKtSAvyNP
2z73A  ( 272 )    lSWspYAvvAllAQfgplew---------VtpyaAQlpVMfAKaSaihNP
                  aaaaaaaaaaaaaaa                aaaaaaaaaaaaa   aaa

                           360       370       380       390       400 
3uon   ( 438 )    acYalcnatFkktfkhllm                               
4dajA  ( 541 )    vcYalcnktFrttfkt                                  
3rze   ( 466 )    liYplCnenFkktfkrilhi                              
2rh1   ( 324 )    liYc-rspdfriAfqellcl                              
2vt4A  ( 341 )    iiYc-rspdfrkAfkrlla                               
3pblA  ( 381 )    viYttfnieFrkAflkilsc                              
2ydv   ( 286 )    fiyAyrireFrqTFrkiirshvlrqqepfkaa                  
3v2w   ( 309 )    iiytltNkemrrafiri                                 
3oduA  ( 300 )    ilyaflgakfktsaqhalts                              
1u19A  ( 304 )    viYimmnkqFrnCmvttlccgknplgddeasttVsktetsqvapa     
2z73A  ( 313 )    miYsvsHpkFreAIsqtfpwvLtccqfddketeddkdaeteipage    
                  aaaaa  aaaaaaaaaa

  • Internship Project - A fully Open Chemically Searchable ChEMBL

    For a long time now we have been keen to release a full and freely deployable version of the ChEMBL database with compound search capabilities built in. This has been possible in the past, but complicated by commercial licenses associated with either the databases or the chemical cartridges. There are now a number mature Open Source chemical toolkits available, such as the excellent CDK, and RDKit.

    So with that brief bit of background there is now an opportunity for an intern to work in the ChEMBL group on the project for 2-3 months. The idea is will be to setup a process which:

    1. Creates a PostgreSQL version of the ChEMBL database (database required by RDKit).
    2. Install the RDKit chemical cartridge.
    3. Migrate this setup to Amazon Web Service public image.
    4. Migrate existing (or new) ChEMBL interface to run off new database and package this up into AWS image.
    5. Develop scripts to allow new releases of ChEMBL to be processed and uploaded as a new AWS image.
    Actually some work has already been done in the public domain, and this will act as a good starting point for someone wanting to learn more about the data and technologies.

    If you are looking for internship this year and have interest in the area of cheminformatics tools and some relevant experience please get in touch (as potential interns, we appreciate you may not have years of industry experience, but we would require you to have previous experience with relational databases and be competent in at least one programming language). Mail us!