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We describe a powerful new method using DNA deep sequencing to optimize protein affinity, specificity, and function. This method was applied to computationally designed inhibitors of Influenza Hemagglutinin to rapidly optimize their sequences for function.
We developed a new computational method for designing protein interactions and applied it to the design of anti-flu hemagglutinin inhibitors. The proteins were designed using computational resources generously provided by Rosetta @ Home participants and inhibited the function of the hemagglutinin flu coat protein that is crucial for viral infectivity. An experimentally determined molecular structure of the designed protein interacting with Spanish flu hemagglutinin (Figure) shows unprecedented level of agreement between model and experiment for a designed interface.
The Whitehead lab is officially open for business.
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