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Control of Protein Conformations


Program Manager: Mildred Donlon, Ph.D.

Detection of biological warfare agents relies on the use of proteins that have affinity for the target of interest and sufficient selectivity to detect the target in the presence of multiple agents or interferants.  Both affinity and selectivity are directly related to the conformational state of the protein.  This program sought to develop entirely new technologies for controlling the conformational states of proteins in real time for the purpose of real-time control of protein function.  The end goal was to develop tunable biosensor systems that provide the ability to vary the affinity and selectivity of the protein to multiple biological warfare targets and interferants or to provide a range of sensitivity that could be adapted to the threat level.  The first phase of this program demonstrated the ability to modulate affinity and selectivity in real time by exposing engineered proteins to a stimulus that controlled their conformational state and using single-molecule measurements to quantify the modulation in protein function.


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