A Critical Piece of the Syrrx Drug Discovery Machine
Syrrx, Inc. is a high-throughput rational drug discovery company committed to redefining the way medicines are discovered. The San Diego-based company has developed automated systems for high-throughput X-Ray crystallography which enable the determination of protein structures more quickly, reliably, and economically than has been previously possible.
With a map of the protein's structure, scientists can then design small molecules which dock on the protein's surface, inhibiting their function. Syrrx's automated approach to structure determination is used in combination with other computational drug discovery methods to identify potentially potent drugs.
The gene-to-drug process that Syrrx has assembled relies at every stage on specific expertise dealing with a mix of scientific and technological disciplines. For the resulting system to be effective and state-of-the-art, each link in the process needs to be built with the most advanced tools available for each function.
The storage, retrieval, and manipulation of chemical information at Syrrx require the application of some of the most advanced informatics tools in modern computing. In the process of designing drugs, queries are run against databases containing millions of molecules. The resulting data accumulates rapidly at exponential rates. The methodologies and techniques used to manage these molecular structures in silico - known as cheminformatics - are therefore a critical component of the Syrrx gene-to-drug process.
THE PROBLEM
Mike Tennant, Ph.D., Director of Computational Biology, at Syrrx who has helped design the company's cheminformatics systems, faced a number of problems when searching for an industrial-strength chemical information database to meet the requirements. Ideally the system would be tightly integrated with Oracle, which is already used throughout Syrrx. It would also require additional sophisticated cheminformatics capabilities.
Scientists and researchers at Syrrx were already using programming tools developed by Daylight Chemical Information Systems, Inc. The functionality of the Daylight toolkit is powerful, however, these tools were designed for implementation by developers and have traditionally required a high level of scientific expertise not found throughout all divisions of an organization. Dr. Tennant wanted the features and performance of Daylight, but not the learning curve or the complexity in their usage.
He also wanted access to a data-rich environment via a web interface, or potentially several different web interfaces to facilitate usage. With such a vast array of data, different teams at Syrrx would want to access information in new and different ways. Flexible web interfaces would provide the ability to create access to the data that could be suited to match specific strategies and scenarios.
There would also be an ongoing need to seamlessly implement and integrate new techniques and tools. As discovery methods evolve, new cheminformatics strategies demand new tools and applications which need to be integrated into existing systems. A system that will remain scientifically vital needs to accommodate and integrate innovation as quickly and seamlessly as possible. This requires an "open architecture" which can accommodate change with minimal or no disruption.
A system that would be easy to use, with flexible web interfaces, that could be adapted to scientific advancements, and which would be fully scalable with high performance: this was Dr. Tennant's target.
Dr. Tennant explored several other software vendors in the cheminformatics market, yet none of these companies offered solutions which were open and extensible or which supported change easily. There were other problems identified as well, such as poor performance, lack of tight integration with Oracle, and doubts about product maturity and expandability.
So Dr. Tennant went back to Daylight with the specifications. They were already prepared for his requirements. Anticipating the need for systems of this caliber, Daylight had been developing DayCart®, a chemistry cartridge which extends an Oracle environment with complete chemical intelligence. All the cheminformatics capabilities of Daylight's research tools are available in the cartridge, yet it can be deployed across entire corporations and accessed via customized interfaces from any desktop.
THE SOLUTION
DayCart® proved to be precisely the system for which Dr. Tennant was searching. The cartridge is a fully integrated set of tools with chemical utilities (normalizations, data conversions, similarity and substructure searching on molecules and reactions) that supply the pieces required to manage chemical data in an Oracle database.
DayCart's® architecture and design integrates with the Oracle server in a fully compatible fashion. There is no need for any external components (legacy systems) to operate. Database administrators can manage chemical information in the Oracle database just like any other data; as their administration tools now understand and support chemistry.
Oracle provides application programming interfaces (APIs) in the database server, allowing third-party developers to work in the internals of the database and add new functionality at that level. Companies can now share chemical information across the enterprise and integrate it with information from other divisions via Oracle databases.
The advantages of DayCart® were clear to Syrrx: the cartridge is flexible, extensible, has the ability to add new cheminformatics techniques using Daylight Toolkits, is tightly integrated with Oracle, can be administered and managed with standard Oracle commands, and is proven to have the fastest performance available. Evaluation completed - DayCart® was the choice. Next was choosing the platform.
Why DayCart® was Chosen to Handle Syrrx's Cheminformatics
- Flexible
- Extensible
- Ability to add proprietary algorithms using Daylight Toolkits
- Tightly integrated with Oracle
- Industry proven
- Validated results
- Standard SQL interface
- Can be administered and managed
- Adaptable performance to meet Syrrx needs
Since Syrrx also needed a completely reliable and expandable platform on which to install DayCart®, the evaluation shifted toward choosing a well-planned architecture from which to serve the application and data. Basically, Syrrx needed to do what many people in IT are trying desperately to do: leverage available hardware and software; focus on what is relevant to the problem; not commit to a closed platform solution; and not reinvent the wheel. Syrrx required a solution that they will be able to depend on for service and support; needed to work with solid businesses whose survival was guaranteed; and required tools that could help them do things in a visual way.
Given these demands and the current landscape of the industry, Syrrx chose to implement DayCart® using Oracle 8.1.7 running on a Sun Solaris system. Oracle is the acknowledged market leader in fully-supported, commercial, relational-databases in the Life Sciences industry. Sun is known throughout the life sciences industry as the platform of choice based on its stability, scalability, service and support for mission critical applications.
Syrrx also chose to implement BEA WebLogic for their Java application server. BEA WebLogic features a three-tier server architecture, incorporating a presentation layer, functional layer, and back-end tier. This multi tier architecture is designed to support the separation of these layers at the development stage, as they require three different sets of skills. Interface designers using HTML build interfaces at the presentation level; analysts design the specific processes and define the functional layer; and developers and IT staff build, install and maintain customized applications on the back end. In addition, BEA, Oracle, and Daylight are all strong partners of Sun and members of their developer community.
Finally, to create elegant interfaces to the system, Syrrx used Sun's J2EE technology. A primary focus of the design was on the use of Java patterns, best practices, design strategies, and proven solutions using the key J2EE technologies including JavaServer Pages (JSP), Servlets, Enterprise JavaBeans (EJB), and Java Message Service (JMS) API. Other ancillary technologies like JDBC are also utilized as relevant to their usage in these patterns which promote "best practices" in the overall design. These standardized, modular, and re-usable components automate many of the time-consuming and difficult tasks of application development. J2EE allowed Syrrx developers to focus on achieving much greater functionality with the system, rather than draining critical time on custom application development. The use of Java Server Pages (JSP's), Servelets, and Beans helped to accelerate and standardize the development effort to implement the overall system.
The design effort followed a 5 tier model (Java Pattern) which consisted of the following layers:
- Client Tier (Application Clients, Applets, and other GUI interfaces)
- Presentation Tier (Single sign on, session management, and content creation, format & delivery)
- Business Tier ( Business logic,transactions and data services)
- Integration Tier (Resource adapters, legacy, external systems, rules, engines,and workflow)
- Resource Tier (Resources, data, and external services)
SUMMARY
The gene-to-drug process at Syrrx requires some of the most advanced informatics tools in modern computing. To handle the complex process of storing, retrieving and manipulating complex chemical structure information, Syrrx has implemented DayCart®, Daylight's chemistry cartridge which extends an Oracle database environment with complete chemical intelligence.
Installed on the Sun Solaris platform, DayCart® is served via BEA WebLogic's multi-tier server architecture while Sun's J2EE technology enables the addition of elegant interfaces which give specific access to a wide range of data for ease of use and improved productivity.
This powerful system is now an integral part Syrrx's information system, and plays a critical role in their drug discovery efforts and search for new drug candidates. It more than meets the existing requirements, and is extensible enough to expand and integrate additional future applications that will include several proprietary functions.
About Syrrx, Inc.
Syrrx, Inc. is a drug discovery company committed to redefining the way medicines are discovered. Based in San Diego, CA, the company is at the forefront of high-throughput rational drug discovery. Syrrx intends to leverage high-throughput structure determination, high-throughput screening, combinatorial and medicinal chemistry together with computational methods to discover novel small molecule preclinical drug candidates. This process enables a unique "gene to drug" platform based on the ability to perform high-throughput rational drug discovery. Syrrx has structural proteomic and drug discovery collaborations with industry leaders, including Sankyo Co. Ltd., Hoffman-La Roche Ltd., Pharmacia Corporation, Celera Genomics, and Cubist Pharmaceuticals. The company has also acquired small molecule assets from Onyx Pharmaceuticals for use in the internal discovery programs at Syrrx. For more information, please visit the Syrrx website.
About Daylight Chemical Information Systems, Inc
Continuously providing the highest performance chemical information processing systems since 1987, Daylight is widely regarded as the leading chemical informatics innovator in the life science industries. Using Daylight tools, researchers and information architects can assemble the ideal chemical information system for any project, regardless of the scale or functionality. Working closely with scientists throughout the life science industries to tackle emerging informatics problems, Daylight facilitates the development of this branch of science while serving the needs of its customers. Daylight CIS, Inc. is a privately held company with corporate offices in Mission Viejo, CA, and research offices in Santa Fe, NM, and in Cambridge, England. For more information, please visit the Daylight Web site at http://www.daylight.com.
About Sun Microsystems, Inc.
Since its inception in 1982, a singular vision "The Network Is The Computer" has propelled Sun Microsystems, Inc. (Nasdaq: SUNW) to its position as a leading provider of industrial-strength hardware, software and services that power the Internet and allow companies worldwide to take their businesses to the nth. Sun can be found in more than 170 countries and on the World Wide Web at http://sun.com.
About Oracle
Oracle is the world's largest enterprise software company. For more information about Oracle, visit their Web site at http://www.oracle.com.
About BEA Systems, Inc.
BEA Systems, Inc. (Nasdaq: BEAS) is the world's leading application infrastructure software company, providing the enterprise software foundation for 13,000 customers around the world, including the majority of the Fortune Global 500. BEA and its WebLogic® brand are among the most trusted names in business. Headquartered in San Jose, Calif., BEA has 91 offices in 33 countries and is on the Web at www.bea.com.
Contact:
Peter Nielsen
Daylight CIS, Inc.
(802) 223-9831
peter@daylight.com