Predicting protein evolution earns Clemson chemist $588,000 NSF award

Published: April 27, 2010

Brian Dominy image by: Clemson University

CLEMSON — When molecules interact, they sometimes behave like they have minds of their own.

Getting into the minds of those molecules is the job of Brian Dominy.

A computational chemist at Clemson University, Dominy tries to calculate how molecules — especially the proteins that are the biochemical workhorses of the human body — will adapt and change when they meet new partners, such as medicines.

His work modeling how proteins evolve in the body has just earned Dominy a five-year, $588,000 National Science Foundation grant to create new computer models of the process.

"If you know how proteins evolve, you can evaluate a drug before putting it in production to see how effective it will be," said Dominy, an assistant professor of chemistry whose National Science Foundation Faculty Early Career Development, or CAREER, award is one of seven such grants the department has earned in the past 10 years.

"What is taking place is a very small and rapid scale of evolution," he said. "A single mutation — or five or 10, but still a relatively small number — can alter the protein slightly so that a drug will no longer bond with the enzyme, but the enzyme can still carry out its normal function. We're trying to understand the physical chemistry underlying those changes and create computer models to predict this mode of molecular evolution."

Unraveling the evolution of proteins also means understanding how they move. That's easier said than done with protein molecules, which essentially are globs of tiny amino acids.

To get a snapshot of how those molecules behave, Dominy turns to laboratory chemists who use techniques like X-ray crystallography and nuclear magnetic resonance spectroscopy to identify the atomic positions in the protein. He then takes this lab data and plugs it into equations in the computer to see how the atomic movement might change over time or under different circumstances.

"There's a lot of motion going on with the atoms and molecules," Dominy said. "Proteins perform a lot of the work to keep cells running, and part of the reason they are able to do this work is because they move. These programs help us figure out how they move and ultimately how they function.

"We work in the classical laws of physics," he said. "We describe them with relatively simple equations — simple for the computer, anyway. They can describe the dynamic behavior of molecules, how they move around."

Crunching the numbers in those equations requires computing power with a little more muscle than your average laptop. That's where Clemson's supercomputer comes in.

Ranked by The TOP500 Project as the 40th most powerful supercomputer in America — and 79th on Earth — the Clemson "condominium cluster" gives Dominy the processing prowess that computational chemistry requires.

"We're particularly thankful to the university for the investment it has made in computing," Dominy said. "Three years ago, Clemson made a commitment to greatly improve the computational infrastructure. That is one of the reasons we have been as successful as we have. They have been continually upgrading it over time. It has been the engine driving the research in our group forward."

Dominy's CAREER grant will repay the favor in part. A portion of the grant money will be used for computer infrastructure. However, the bulk will be devoted to student research and instruction, both at the graduate and the undergraduate levels. One of the key components of his grant proposal is to develop new, multidisciplinary instruction in "chemical biology" and "biophysical chemistry" that bring fresh perspectives to science students — and future researchers — earlier in their careers.

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This material is based upon work supported by the National Science Foundation under Grant No. MCB-0953783. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.