A number of important biological processes involve structural changes which modify the chemical behavior or function of the active molecular agents (e.g., allosteric regulation of substrate binding). These structural transitions generally involve a highly directed process in which small amounts of input energy can lead to correlated displacements involving thousands of atoms. The vectorizing force for the motion presumably originates from the three-dimensional structure of the molecule in question. In this sense, there is a deterministic aspect to the motion, superimposed on top of the random thermal fluctuations.

This Account will focus on recent developments in our understanding of functionally important protein motions from a dynamics point of view. The emphasis will be on the use of optical methods to probe the protein motion directly in the time domain. In this application, phase grating spectroscopy has proven to be extremely sensitive to energy and structural relaxation processes. This spectroscopy is an extension of transient grating methods in which the protein’s motion is holographically recorded in real time to give a direct probe of the protein strain and the accompanying energetics, two fundamental parameters needed to understand the mechanics of the motion.