A Technique to Unfold and Refold Proteins through Clathrate Hydrate Formation

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The Principal Investigator (PI) proposes to develop a new technique to unfold wrongly folded proteins and to refold them to their native and active conformations. The technique involves the formation of clathrate hydrates in protein-containing solutions with low concentrations of denaturants. Hydrate formation in such solutions opens up the possibility of an in-situ control of denaturant concentration by converting part of the aqueous phase to a solid crystalline form. The desired objective is to unfold proteins by forming hydrates and thus increasing denaturant levels, and subsequently refold these proteins correctly by dissociating hydrates and thus reducing denaturant levels. This research is exploratory in its nature, and is based on a well-known technology directed towards a completely new application.