SynPharm: An electric ‘vade mecum’ for manipulators of biological signaling

‘Pharmacology is benefited by the prepared mind. You need to know what you are looking for. Most discoveries even today are a combination of serendipity and searching.Siddhartha Mukherjee

For researchers wanting information, the Internet is both a blessing and a curse. It has given us access to incredible amounts of data at astonishing speeds, which should be A Good Thing. The problem is that accessing online material can sometimes feel like requesting a drink of water and receiving a tanker-load, full in the face, from a fire hose. The issue is not just one of quantity but also of quality: which data come from really well-considered sources, and which come from automated text mining of the sort that classes ‘kidney bean mosaic virus’ under ‘nephrology’? The problem is particularly acute for researchers wanting to choose the best small molecule to manipulate a biological pathway, given the vast repositories of medicinal chemistry on the web and the intense use of text mining and machine learning.

 A few years ago, two organizations with a strong interest in providing high-quality pharmacological information decided to collaborate to produce an open, expert-curated database, the Guide to Pharmacology. One of these organizations was NC-IUPHAR, the Nomenclature Committee of the International Union of Basic and Clinical Pharmacology. NC-IUPHAR is the body in charge of agreeing nomenclature of ligands (‘drugs’ and research compounds) and their targets, doing so via a large number of committees comprising, in all, over 900 experts. NC-IUPHAR had a clear need to provide an accessible resource on nomenclature and on ligand-target interactions, to make it easy for authors to name things correctly and not confuse the literature with a plethora of synonyms and confusions about what binds what.  The other organization was the British Pharmacological Society, which already published a regularly updated, paper-format Guide to Receptors and Channels as a special issue of the British Journal of Pharmacology. The two organizations decided to combine their resources into a single on-line database, built and run at the University of Edinburgh’s Medical School, with additional support from the Wellcome Trust.

The database (shown below and open to anyone at www.guidetopharmacology.org) currently contains information on 2,808 human targets and 8,872 ligands that interact with them. It can be searched in many ways, including by ligand, by target, by family, by relevance to disease, and even just by a Google-style text query. A large range of links allows users to see detailed information, for example on gene structure or expression patterns, held in other databases. In turn, a range of other online resources connect to and draw data from the Guide to Pharmacology. The Guide is not the largest database by any means, but what makes it different is the care taken to source data from sound, peer-reviewed publications (ideally with clear confirmation from another source), and to have the data scrutinized by the NC-IUPHAR committees composed of real people who are leaders in that precise field.

 

Readers of the British Journal of Pharmacology or the British Journal of Clinical Pharmacology will already be familiar with the Guide, as all recent papers in those electronic journals connect every mention of a ligand or target with the appropriate entry in the Guide to Pharmacology, so that a reader can click straight through to gain detailed information. What is more, the BJP’s two-yearly publication of its Concise Guide to Pharmacology is produced as an extract of the database converted into human-readable form. Indeed, except for the text introductions to each section, the Concise Guide is produced automatically from the database using some experimental automatic authoring software written by Peter Buneman and colleagues at the University of Edinburgh’s School of Informatics. Like the database itself, pdf copies of The Concise Guide to Pharmacology are available free of charge here. They are also distributed at selected conferences in the developing world in the form of memory sticks and similar devices, so that the information can still be accessed where Internet service is not reliable.. A limited number of paper copies is also produced for the same purpose.

The nature of a fast-moving subject like pharmacology is that work like this is never completed. With help from a range of subject experts, the Edinburgh team is currently building a new resource, the Guide to Immunopharmacology. This includes both immune-derived effectors (biologicals such as antibodies etc.), and ligands and targets that modulate the immune and inflammatory systems. All of the data can be accessed via the normal Guide to Pharmacology portal but it will also be accessible via a new ‘immunologist-friendly’ portal, currently in beta (test) release. We hope that this approach will encourage people trained in other fields such as immunology to make more use of pharmacological data.

The database also has a new portal designed to help synthetic biologists and protein engineers find natural drug-binding sites that might be ‘borrowed’ and incorporated into engineered proteins to make these, too, responsive to the drug. This resource, SynPHARM, is also available free to everybody at the SynPHARM site.So, if you want to find a ligand that can modulate a favorite pathway or target, or you want to know about likely on- and off-target effects of a drug, or you want a tutorial about classes of ligands or targets, or you just want to keep up with the developments by reading the ‘hot topics’ blog, come and visit the Guide to Pharmacology. And please contact the team who run it to tell us what you think.