Models derived from X-ray crystallography can give the impression that proteins
are rigid structures with little mobility. NMR ensembles may suggest a more dynamic
picture, but even these represent a rather narrow range of possibilities close to the lowest
energy state. In reality proteins participate in a wide range of dynamics from the subtle
and rapid sidechain dynamics that occur in nanoseconds in the PDZ signaling domain to
the large and slow rearrangement of secondary structure that takes days in the mitotic
checkpoint protein Mad2. Between these extremes are motions on time scales typically
associated with protein function, such as those in SNase monitored by hydrogen
exchange. The dynamic character of several protein systems, including PDZ domain,
Calmodulin, SNase, and Mad2, were explored using a variety of biophysical techniques.
This broad investigation demonstrates the dynamic variability between and within
proteins. The study of PDZ and Calmodulin illustrates how a computational technique
can recapitulate experimental results and provide additional insight into signal
transduction. The case of SNase shows that HX NMR data can be exploited to reveal
protein dynamics with unprecedented detail. The Mad2 system highlighted some of the
pitfalls associated with this technique and some alternative strategies for investigating
protein dynamics