ChemNews.Com VOL 9 NO 2

RiboTargets, a biopharmaceutical drug discovery company in the United Kingdom, desired to assist their scientists in data collection and analysis. By connecting their Oracle database with ChemOffice WebServer, they have successfully created such an information management system. The fact that their scientists can intuitively use the system with tools that they are already familiar with, like ChemDraw, is one more reason that RiboTargets is raving about its new found technology.

The Drug Design Group at RiboTargets From left to right: Dr. Philippe Vaglio, Dr. Dave Morley and Dr. Mohammad Afshar

Virtually all drug discovery efforts focus on protein targets because, until recently, the technology for developing small molecules that could achieve high binding specificity to RNA, the key intermediate in protein synthesis, was not available. RiboTargets is the first biopharmaceutical company to focus exclusively on the development of drugs that target RNA.

The determination of the three dimensional structures of RNA and the nature of its interactions with drugs by NMR are central to RiboTargets' strategy for the rational design of inhibitory compounds. With only a handful of academic groups in the world capable of effectively competing in this field, RiboTargets is the first to evolve into a commercial drug discovery company. RiboTargets has a broad in-house technology platform with capacities in combinatorial chemistry, drug design, high throughput screening, molecular biology, and structural biology.

Creating a New Tool

Likes most research institutes, RiboTargets lives by its information systems and the inventive thinking goes well beyond the bench. Dr. Mohammad Afshar, Head of Drug Design at RiboTargets, along with Dr. Philippe Vaglio, have created a "best-of-breed" system used for managing their discovery data, compound registration, assays, and analysis.

"It is important that the scientists use tools they are familiar with," says Philippe. "They want to learn about chemistry and biology, not how to operate an information system."

We didn't want to change the foundation of our IT system, but we wanted to add a chemical searching component.

When depending on analysis of data from RiboTargets HTS and combinatorial chemistry labs, data collection from the bench is vital. "We can't afford to miss data. So the system has to be friendly, but also has to be thorough." According to Dr. Afshar, "the system we've designed, and are continuing to refine, mirrors the scientist's workflow. The web interface is a great start, and the system asks questions, collects data, and process information in a way that follows what the scientist did at the bench."

Oracle Connectivity

The heart of the system is an Oracle database running on high-performance SGI servers. The Oracle system maintains the data tables and structure. It is the official repository for all RiboTargets information. At the user interface is a standard WWW browser, such as Netscape or Internet Explorer, utilizing the ChemDraw Plugin for chemistry features.

Dr. Afshar continues, "When we saw the ChemDraw Plugin, we knew we needed it in our environment. By allowing the chemists to draw directly into the web page without leaving the browser, the ChemDraw Plugin maintains data input on one screen. The scientists don't need to learn a new tool to draw chemicals, and there's no desktop software to maintain."

As Oracle doesn't understand chemistry, and you can't convert a structure query to SQL, there was some software needed to make the system chemically aware. RiboTargets turned to CambridgeSoft and asked if it was possible to add chemical structure searching to their Oracle system.

Chemical Searching

"We didn't want to change the foundation of our IT system," says Philippe, "but we wanted to add a chemical searching component." The answer was the ChemOffice WebServer. Although it works as a stand-alone chemical data server, the ChemOffice WebServer is entirely open, and allows various components to be connected to other systems. RiboTargets installed a ChemOffice WebServer on a high-performance Windows NT machine as chemical search index to the Oracle data.

According to Philippe, the process of connecting ChemOffice WebServer and Oracle was straightforward. "The ChemOffice WebServer is written largely with standard ASP and exposes all of the chemical search functions. It was easy to connect the search logic with our Oracle engine." RiboTargets uses Perl as their primary scripting language. "Talking to the ChemOffice components with Perl was straightforward. The project took about two days to achieve a functional prototype."

From a technical standpoint, the architecture of the system has hardly changed from the original Oracle design. All data, including chemical structures, are stored in the Oracle database. When a record is added that contains a structure, a new record is created in the Oracle table and in a parallel ChemFinder table. The ChemFinder table then serves as a search index to search chemicals in the Oracle database.

When a search is submitted, the chemical query happens over the ChemFinder table. This returns a set of numerical IDs. The IDs are repackaged and sent along with the rest of the SQL query to the Oracle engine.

The Future

"We're going to continue to add chemical intelligence to all of our operations," says Philippe. "Right now we're examining everything we do and looking at both productivity and analysis gains that can be achieved with this technology. The scientists' responses have been very positive. They like the user interface and they don't notice the back-end technology. I suppose that's the best result we could have."