Dynamically Driven Protein Allostery Exhibits Disparate Responses for Fast and Slow Motions.

There is considerable interest in the dynamic aspect of allosteric action, and in a growing list of proteins allostery has been characterized as being mediated predominantly by a change in dynamics, not a transition in conformation. For considering conformational dynamics, a protein molecule can be simplified into a number of relatively rigid microdomains connected by joints, corresponding to, e.g., communities and edges from a community network analysis. Binding of an allosteric activator strengthens intermicrodomain coupling, thereby quenching fast (e.g., picosecond to nanosecond) local motions but initiating slow (e.g., microsecond to millisecond), cross-microdomain correlated motions that are potentially of functional importance. This scenario explains allosteric effects observed in many unrelated proteins.