Researcher Aims for Faster, More Accurate Drug Discovery

As the recent H1N1 (swine) flu scare has reminded the world, it’s critical to find new drugs that effectively treat all of the potential mutations of a virus.  But drug discovery is an arduous and expensive process.  Michael Shirts, assistant professor of chemical engineering, aims to simplify drug design through the use of advanced computing methods.

From an early age, Shirts has been intrigued by what happens at the nanoscale. “I think it’s remarkable that almost all of the biological activities—the physical properties we observe in everyday life have to do with the motions and interactions of molecules at a very small scale,” he says.

Shirts uses computer simulations to understand molecular behavior.  His research may inform the design of new materials—particularly new drugs.  He recently won a $50,000 FEST Distinguished Young Investigator grant for his proposal to build tools that can enable the development of antimicrobial drugs with enhanced resistance profiles. 

Traditional drug discovery has relied largely on a trial and error approach.  “One of the big roadblocks in drug development is that if you want to test a new drug to see if it will work, you have to make it first,” says Shirts. 

Computer simulations can model intricate molecular interactions and help researchers identify potential treatments with a higher degree of accuracy and speed.  A virus is essentially a small nanomachine, Shirts explains.  Through complex computer simulations, his ambitious plan is to create tools that help design molecules that bind to the gears of a virus or bacteria to shut it down.

Shirts admits that current computational tools, though sophisticated, are not quite ready for such design challenges.  “This research takes a tremendous amount of computer power, and even then doesn’t always give correct answers,” notes Shirts.  “Current methods still need a lot of work.  But if the problem could be solved already, it wouldn’t be that interesting to study!”

As computing power increases, the possibilities expand.  Shirts is on the cutting edge of this expansion, with his participation in a unique distributed computing project called Folding@home.  Through the project, people from around the world can volunteer personal computing power to help researchers run complex problems.  In just 20 days, Shirts received 300,000 results packets through the project.  “Since each packet takes 2-3 days worth of work, this is the equivalent of 30,000 computers working on these problems full time,” he says.

This research holds great promise, not only for the design of new antimicrobial drugs but also for other critical areas of drug design, such as targeted anticancer treatments and personalized medicine. 

In addition to receiving the FEST award, Shirts’ research will also benefit from his winning a $10,000 Oak Ridge Associated Universities’ 2009 Ralph E. Powe Junior Faculty Enhancement Award.  He received this award for developing a benchmark for methods that compute the strength of molecular interactions.  With this benchmark, it will be much easier for researchers to identify which methods they should use when designing small molecules that act as drugs.