Chemistry Reference
In-Depth Information
9
Protein Dynamics and Interactions
Ted A. Laurence and Shimon Weiss
9.1
Introduction
9.1.1
The Single-molecule Approach to Protein Dynamics and Interactions
Proteins are amazingly versatile, serving as motors, enzymes, messengers, and
structural elements in all living things. They operate in the still less familiar
nanometer-scale (mesoscopic) world, with dimensions smaller than the macroscopic
world, but larger than the world of quantum mechanics. Although proteins are
small, many concepts from the macroscopic world may be used. Comparisons of
protein machines to objects of classical mechanics (rotors, motors, structural
elements) are often made, and many experiments have veri
ed the validity of such
comparisons [1
-
4].
The primary difference between the world of macroscopic machines and
nanometer-scale machines is that random thermal motion within the machines
cannot be averaged out to thermodynamic quantities. The random structural
fluctuations of proteins are often intrinsic to their operation. Also, protein function
often involves repeated chemical reactions involving single molecules of substrates.
Along with the deterministic component, there is a stochastic, or random nature to
the timing of the protein function. Non-equilibrium statistical mechanics methods
must be used to describe the dynamics of these machines.
To probe nanometer scale
fluctuations experimentally requires methods that
either synchronize, or in the case of single-molecule spectroscopy, isolate molecules.
Non-equilibrium methods, such as fast mixing, nanosecond laser heating, time-
resolved
fluorescence, femtosecond spectroscopy can create a temporary, non-
equilibrium state. Observing the molecules in the non-equilibrium state as they
relax back to equilibrium, probes the
fluctuations. An alternative method used to
create a non-equilibrium state is the spontaneous
fluctuations present in the system
even at equilibrium;
fluorescence correlation spectroscopy (FCS) is an example [5].
