ChEMBL

EU-OPENSCREEN

A brief link to a developing project under the ESRF Research Infrastructure Roadmap - EU-OPENSCREEN. The basic idea is to develop and establish an underpinning infrastructure in a pan-European setting to allow screening and chemical tool identification for new, therapeutically/commercially unvalidated protein targets. This is a fantastically important project at the current time, both scientifically and economically, so I hope you also are interested in it's progress.

Hit the sack - Pt. VIII - Best Western Berlin-Mitte, Berlin

A small city centre hotel in Berlin, one of my favorite cities. I arrived in the dark, and left in the dark, but it was great; quick checkin, helpful staff and a quiet room (no night-clubs, pubs, or street-fights outside). Truly restful. Near to the hotel is the excellent book/cd store Kulturkaufhaus Dussmann.

Hotel web site

Overall a sunny score of 67%. An excellent city centre choice for a travelling scientist.

DrugStore - An Overview

DrugStore is a database of drugs - both small molecules and biologicals. It is quite small, but complex, since drugs and the way they work are surprisingly complex. The basic content of DrugStore is three domains -

Chemistry., the 2-D structure of the drug, and in the case of biologicals the sequence. We also take care of the case where the dosed drug is a prodrug (a case where the dosed ingredient is essentially inactive, and a metabolic transformation is required to generate the active form). Given this data, it is then trivial to calculate a large number of compound associated properties (MW, clogP, etc.).

Biology, the mechanism of action and the molecular target of the drug. This is surprisingly complicated, for many drugs there are complex modes of action, or cases where the target assignment is still tentative, here we have a confidence score for the target assignment. We are also careful to only include targets that are responsible for the clinical efficacy of the drug, since many drugs bind to serum albumin, but you wouldn’t really want to include that as a drug target. Where possible, we also include the binding domain for the drug within its target, alongside PFAM domain, etc.

Medicine, what the drug is used for, and its properties, for example included are things like black-box warnings, withdrawn status, etc. We include a number of ontologies (well to use the word ontology here is a bit of a stretch) to describe the therapeutic application of a drug. We also differentiate between genuine therapeutic agents, imaging agents, and non-therapeutics - this has the number of therapeutic drugs appear smaller than sometimes thought.


 Sprinkled across the database are properties like the dosage size, dosage form (oral, topical, parenteral, etc), pharmacokinetic properties, trade names, various approval dates, full package inserts, etc., etc. There are many things we have been asked for in the past, like quantitative side-effects, biomarker data, pharmacogenetic data, adventitious pharmacology, detailed toxicology data, sales revenues, but there is no simple way to consistently harvest these data, and other resources (unfortunately often proprietary) cover some of these areas incredibly well. We also store some data within our curation schema that we cannot (currently) distribute due to copyright restrictions, however, these additional data would be available to interested collaborators.

We are developing a plan to integrate the data within DrugStore within some other public databases that address drugs and drug action, and to eventually tightly integrate the most interesting features into CandiStore, treating launched drugs as Phase IV agents.

Since there are so few drugs launched, keeping DrugStore up to date is quite straightforward, and we plan to post data for new drug approvals on the ChEMBLog.

Conference - German Chemical Society, Frankfurt, August 30th 2009

We are going to present at an Open Source Drug Discovery Session at the National Meeting of the German Chemical Society, Held in Frankfurt am Main, August 30th to September 2nd 2009. Further details of the meeting are here

Hit the sack - Some Background And Clarification

We post some reviews of hotels that we stay at on our professionally related travels under the Hit-The-Sack tag. These are our personal experiences of a stay at the hotel from the perspective of a visiting scientist (so the views expressed are not those of a typical visitor to the hotel, and may not even be those of a typical scientist!). Over time, they may be useful for trip planning, or just reminding us of some of the good times.

As you would expect, the rooms we stay in are not suites or other types of luxury rooms. The room score and discussion refers to the actual room stayed in for that visit. The dates in the blog reported do not necessarily reflect those that the stay in the hotel occurred. However, we always try and post as contemporaneously as possible.

The pictures of the hotels are (usually) taken from simple Google image searches, and may be covered by copyright. If this is a concern, please contact me, and I will replace/delete the photo.

SARfari - An Overview

SARfari is an integration platform built on top of our databases (StARlite, CandiStore and DrugStore). It also includes an open architecture for the loading of proprietary (or other third party data). This loading is performed against a series of local 'business rules' that define chemical structure representation, target mapping, assay units, etc. The SARfaris are written in the Catalyst MVC framework (so essentially a structured perl), and also Apache for the application server. The original idea was to mirror in an informatics system a 'platform' view of drug discovery - in this case integrated data within a gene family of interest (but it could be around a metabolome-based view, e.g. adenine binding proteins, an entire genome, etc.. Our first foray into the area was in 2004 with a GPCR system built with SQLite, however, this was not very extensible, and we rapidly reached the bounds that were technologically possible. We then built a protein kinase version, and then a rhodopsin-like GPCR SARfari under Oracle, and included the ability to load 'local' data. SARfari is quite neat in that it integrates SAR, sequence alignment, binding site, and 3-D structure data all into a single, simple portal; with, of course, a focus on drug discovery processes. One additional thing we did here was to process patent crystal structures (which often never make it into the RCSB PDB) into a usable form, and then loading these into a version of SARfari.

Our future plans include building a generic SARfari builder (so you will be able to paste a sequence of an arbitrary target into a web page, and then, after a short while, fully integrated and federated data will be delivered, as a new stand-alone gene-family themed web application).

At the EMBL-EBI we will host a copy of kinase SARfari and GPCR SARfari, populated with the relevant public-domain data from our own databases, the software systems (including source code) will be downloadable in toto and gratis, and installable locally for loading of local lab data (we do not plan to allow upload of data onto the EMBL-EBI SARfaris). At the moment, SARfari requires Oracle 9, and the Symyx chemical data cartridge, but future development will be directed towards a more generic and Open Source solution, including the CDK. If anyone would like to try the existing SARfari systems in advance, please feel free to contact us now.

The same software infrastructure and look-and-feel will be used for the DrugEBIlity project at the EMBL-EBI.

Course - Practical Aspects of Small Molecule Drug Discovery

A brief alert to a Wellcome Trust course being held here on campus this July.

And while we are on the subject of conferences, the RSC is organising a meeting on the 1st October 2009 on 'Chemical Tools and Challenges in Systems Biology' to be held in Stevenage in the U.K.. jpo is speaking at this meeting on the ChEMBL project. There is nothing on the RSC website yet, but it looks like it should be a good meeting.

Hit the sack - Pt. VII - Tribeca Grand, New York

A boutique hotel in downtown Manhattan (Tribeca district to be more precise). Convenient for most things from Battery Park, JR on Park, Times Square, Union Square, 5th Avenue, Canal St, Chinatown, the Soho Apple store, and close to the fishing store on 27th St. My favorite place (sort of) to stay in Manhattan, and it is nicer to be in NYC rather than out in New Jersey when visiting. However, the service is slipping over time, and I may well switch to a new hotel the next time I am in The Big Apple. It is the little things - like I always used to get a free hat - a lovely black wool one with 'Grand' written in gold on the front, and their used to be five or six CDs in the room that you could listen to (mostly 'lounge', but hey, what are the chances of finding obscure UK 80's 12 inchers anyway?), but they are no longer there. There was also a child sized T-shirt that was nice. The last time I was there, two things niggled me. 1) Teh internet was a bit of a joke, and 2) when I went down for a drink in the bar, they looked me up and down, and sat me at a really bad table way out of the way. I guess I didn't really fit in with the crowd in there (young, slim and cool, and me, well....). So, I made a point of wearing my Gordon Conference T-shirt everytime I went in after that - it didn't help. The other odd thing that happened when I was there, was that since I was wearing the 'hotel hat' (the same as the bellboys/bellhops) I guess some people thought I was staff, and looked a little perturbed as I confidently ignored them all outside the hotel on my way in and out.

Hotel Web Site

Overall an okeledokele score of 50%. However, not really one for a travelling scientist.....