Profiles of Pioneers: Class of 2004–2009
Homme W. Hellinga, Ph.D.
Duke University Medical Center
“[The Pioneer Award] provided me with the room to tackle a relatively long-term problem in which I had to spend many years building up a new methodological infrastructure.”
Proteins are central to all living things. They provide structure for cells, organs and tissues, and they also run many of the biological machines in our bodies. Protein engineering, a relatively young science, aims to build entirely new proteins with a range of functions. Engineered proteins could be novel drugs, vaccines, enzymes or scaffolding for building damaged or diseased tissues.
Dr. Homme Hellinga’s goal is to develop and test new computational methods for protein design and engineering. Because this field is new and many challenges still impede progress, the Pioneer Award has enabled him to focus on long-term experimental methods development. This endeavor, he says, has opened up important new opportunities.
Hellinga starts with the three-dimensional structure of a protein and uses computational methods to identify genetic changes that will alter the protein’s function in a predictable way.
That is easier said than done: Computer algorithms must sift through a huge number of potential choices, taking into account the shapes of atoms, the chemical bonds connecting atoms, electrical charges, interactions with water, and more. Not surprisingly, Hellinga says, most of the calculations are inaccurate. He estimates that about 1 to 10 percent of the predicted protein sequences are functional “on a good day.”
The Pioneer Award has been ideal for Hellinga’s project, full as it is of unknowns and unpredictable outcomes. He has had to build many proteins, then test them in the lab to identify the ones he wants. The Pioneer Award enabled Hellinga to spend a lot of time developing robotic methods, an effort that proved to be much harder than expected.
After setting up parameters for automation and other aspects of his protein design and engineering work, Hellinga has just built a synthetic protein-engineering pipeline that will enable him to construct and test hundreds of proteins in just a few weeks. He expects to begin collecting data very soon.
Cox JC, Lape J, Sayed MA, Hellinga HW. Protein fabrication automation. Protein Sci 2007;16:379-90.
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