The
process of protein folding is known to involve global motions
in a cooperative affair; the structure of most of the protein sequences
is gained or lost over a narrow range of temperature, denaturant,
or pressure perturbations. At the same time, recent simulations and
experiments reveal a complex structural landscape with a rich set
of local motions and conformational changes. We couple experimental
kinetic and thermodynamic measurements with specifically tailored
analysis of simulation data to isolate local versus global folding
probes. We find that local probes exhibit lower melting temperatures,
smaller surface area changes, and faster kinetics compared to global
ones. We also see that certain local probes of folding match the global
behavior more closely than others. Our work highlights the importance
of using multiple probes to fully characterize protein folding dynamics
by theory and experiment
