Global dynamics behind enzyme catalysis, evolution, and design

Enzymes are inherently dynamic entities, with their functions intricately governed by the interplay between conformational dynamics - ranging from local residue fluctuations to global motions - and biochemical activity. Deciphering how such dynamics coordinate higher-order cooperativity across multiple timescales to drive catalysis remains a fundamental challenge. This mini-review highlights the role of large-scale, collective motions involving domain-level displacements and hinge-based rearrangements, which not only facilitate substrate recognition, transformation, and release, but also emerge from and propagate through multidirectional allosteric interactions. Such dynamic mechanochemical coupling reflects evolutionary memory and provides a blueprint for enzyme design innovations.