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AbstractMost functional processes of biomolecules are rare events. Key to a rare event is the rare fluctuation that enables the energy activation process, which powers the system across the activation barrier. But the physical nature of this rare fluctuation and how it enables barrier crossing are unknown. With the help of a novel metric, the reaction capacity pC, that rigorously defines the beginning and parameterizes the progress of energy activation, the rare fluctuation was identified as adoi:10.1101/2021.09.27.462043 fatcat:ekk3223i5zftlk3rfe2hgcxfjm