“…Elucidating the catalytic origin of enzymes, a fundamental question in chemistry, guides the development of engineering strategies to create function-enhancing enzyme variants for chemical synthesis, − waste degradation, − fuel production, − disease diagnosis, and treatment. − Protein dynamics, which ranges over 10 orders of magnitude in timescale, − has been widely reported to mediate catalysis. ,,− For example, residue vibrations and collision have been proposed to facilitate transition state (TS) barrier crossing on the subpicosecond time scale (e.g., lactate dehydrogenase, alcohol dehydrogenase, and purine nucleoside phosphorylase). − Residue and loop motions have been proposed to facilitate the positioning of substrates to form a reactive conformation (or near-attack conformation) on the pico- to nanosecond time scale (e.g., dihydrofolate reductase, chitinase, β-lactamase, retro-aldolase, Kemp eliminase, glycoside hydrolase, cytochrome P450, and soybean lipoxygenase). − ,− Conformational changes in loops and domains have been demonstrated to enable substrate binding, solvent shielding, or product release on the nanosecond to millisecond time scale (e.g., triosephosphate isomerase and adenylate kinase). ,,, …”