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Illustration of the hydrogen exchange-directed protein engineering approach for populating the partially unfolded intermediate. (a), Unfolded, intermediate, and native states and their free energies revealed by the native-state hydrogen exchange method. The ribbon structures are made using Insight II (Accelrys). The pdb code is 1RIL. (b), Populating the folded region of the intermediate mimic by protein engineering. c, Melting curve of the intermediate mimic.
