teams computers to design drugs
Ted Smalley Bowen ,
Technology Research News
Computational grids provide the raw material
for assembling temporary, virtual computers from sometimes far-flung resources
connected to the Internet or private networks. They came about because
researchers often require processing power, storage, and bandwidth far
beyond the scope of their own systems.
This type of distributed computing, which can also include scientific
instruments, makes the means to tackle complex applications available
on an ad hoc basis, and allows researchers to draw on widely-dispersed
stores of information.
The molecular modeling programs used to design drugs are especially data-hungry
and computationally intensive applications. Designing a drug involves
screening massive databases of molecules to identify pairs that can be
combined, and figuring out the best way to combine them to achieve a certain
affect. The molecules could be enzymes, protein receptors, DNA, or the
drugs designed to act on them.
During this molecular docking process, researchers try to match the generally
small molecules of prospective drugs with the larger biological molecules
they are designed to affect, such as proteins or DNA. These searches can
entail sifting through millions of files that contain three-dimensional
representations of the molecules.
A group of researchers in Australia has put together a set of software
tools to perform molecular docking over a computational grid. The tools
tap into remote databases of chemical structures in order to carry out
the molecular matching process.
Grid computing software finds and accesses resources from networked computers
that can be physically located almost anywhere. It coordinates scheduling
and security among systems that may be running different operating systems,
to combine, for example, the processing capabilities of half a dozen Unix
servers and a supercomputer with databases stored in a collection of disk
drives connected to yet another computer.
The researchers adapted a molecular docking program to work on a grid
configuration by having it run several copies of a molecular matching
program on different systems or portions of systems. The software performed
many computations at once on different subsets of the data, then combined
the results. This type of parallel processing, also known as a parameter
sweep, enabled the grid application to work through the matching process
The complexity of each molecule record and the scale of the database searches
involved in molecular docking put such applications beyond the reach of
most labs' conventional computing resources, according to Rajkumar Buyya,
a research scientist at Monash University in Australia. "Screening each
compound, depending on structural complexity, can take hours on a standard
PC, which means screening all compounds in a single database can take
Even on a supercomputer, "large-scale exploration is still limited by
the availability of processing power," he said.
Using a computational grid, however, researchers could feed extensive
computing jobs to a coordinated mix of PCs, workstations, multiprocessor
systems and supercomputers, in order to crunch the numbers simultaneously.
A drug design problem that requires screening 180,000 compounds at three
hours each would take a single PC about 61 years to process, and would
tie-up a typical 64-node supercomputer for about a year, according to
Buyya. "The problem can be solved with a large scale grid of hundreds
of supercomputers in a day," he said.
To run the docking application on a computational grid, the researchers
developed a program to index chemical databases, and software for accessing
the chemical databases.
To speed the scheme, the researchers replicated the chemical database
so that more requests for database information could be processed at once.
To further speed the process, the researchers wrote a database server
program that allowed computers to field more than one database query at
The researcher's scheme compensates for the uneven bandwidth, processing
speeds, and available resources among grid-linked systems by mapping the
location of files and selecting the optimal computer to query, according
to Buyya. "The data broker assists in the discovery and selection of a
suitable source... depending on... availability, network proximity, load,
and the access price," he said.
Because the performance of database applications suffers over network
connections, the researchers generated indices for each chemical database,
including references to each record's size.
This allowed each computer to respond to queries by first checking the
index file for the record's size and location and then accessing the record
directly from the database file, rather than sequentially sifting through
the database, said Buyya.
The application requirements and the tools used to meet them are specific
to molecular docking, but similar software would speed compute-intensive
tasks like high-energy physics calculations and risk analysis, according
The researchers tested the scheduling portion of their scheme on the World
Wide Grid test-bed of systems in Australia, Japan and the US, and successfully
estimated the time and cost required to run the applications in configurations
optimized for speed and for budget, Buyya said.
Using the test bed, they screened files of 200 candidate molecules for
docking with the target enzyme endothelin-converting enzyme (ECE), which
is associated with low blood pressure.
The researchers' use of grid computing tools to automate molecular docking
is "an excellent application of grid computing," said Julie Mitchell,
an assistant principal research scientist at the San Diego Supercomputer
Center. Features like "deadline- and budget-constrained scheduling should
make the software very attractive to pharmaceutical companies" and to
companies interested in such computationally demanding applications as
risk analysis, scientific visualization and complex modeling said Mitchell.
"There's nothing specific to molecular biology in their tools, and I imagine
they could be applied quite readily in other areas."
The researchers also handled the process management aspects of adapting
the applications to grids well, she added.
"The [researchers'] approach is obviously the way to go for those type
of applications on the Computational Grid," said Henri Casanova, a research
scientist in the computer science and engineering department of the University
of California at San Diego. "The notion of providing remote access to
small portions of domain-specific databases is clearly a good idea and
fits the molecular docking applications," he said.
The economic concepts underlying the scheduling and costing of grid applications
application are still immature, Casanova added. "The results concerning
application execution are based on a Grid economy model and policies that
are not yet in place. There are only vague notions of "Grid credit unit"
in the community and the authors of the paper assume some arbitrary charging
scheme for their experiments. This is an interesting avenue of research,
but...there is very little in terms of Grid economy that is in place at
the moment," he said.
The data access and computation techniques are technically ready to be
used in practical applications today, according to Buyya.
Buyya's research colleagues were Jon Giddy, and David Abramson of Monash
University in Australia and Kim Branson of the Walter and Eliza Hall Institute,
in Australia. The research was funded by the Australian Cooperative Research
Center for Enterprise Distributed Systems Technology (EDST), Monash University,
the Walter and Eliza Hall Institute of Medical Research, the IEEE Computer
Society, and Advanced Micro Devices Corp.
Funding: Corporate; Government
TRN Categories: Distributed Computing; Applied Computing;
Story Type: News
Related Elements: Technical paper, "The Virtual Laboratory:
Enabling On-Demand Drug Design with the World Wide Grid," posted on the
computer research repository (CoRR) at http://xxx.lanl.gov/abs/cs.DC/0111047.
Morphing DNA makes motor
computers to design drugs
Atom clouds ease
Web pages cluster
by content type
alters device motion
Research News Roundup
Research Watch blog
View from the High Ground Q&A
How It Works
News | Blog
Buy an ad link