Chemistry Reference
In-Depth Information
12
Osmophobics and
Hydrophobics
The Changing Landscape
of Protein Folding
Matthew Auton and B. Montgomery Pettitt
CONTENTS
12.1 Thermodynamic Background ....................................................................... 310
12.2 Theoretical Framework ................................................................................. 314
12.3 Simulation Results ........................................................................................ 319
12.4 Conclusions ................................................................................................... 322
Acknowledgments .................................................................................................. 323
Abstract
: We discuss recent experiments and theories concerning protein col-
lapse and folding. Experiments using multicomponent solutions have revealed
much about the mechanism of folding. Simulation and theory have been used
to interpret thermodynamic and fluorescence correlation spectroscopy experi-
mental results. We consider the theoretical arguments using variations of the
free energy with respect to fluctuations in number and composition to consider
recent experiments. We find new measures of protein stability tendencies offer
a different view than the often poorly defined hydrophobic effect.
The underlying questions governing the transition of proteins from their unfolded
state to their native state and recognition between proteins are as relevant now as they
were 50 years ago (Anfinsen 1973). Misfolded (Weinreb et al. 1996) and unstruc-
tured domains (Dyson and Wright 2002, 2005) represent interesting examples of
states where the understanding of recognition, and the self-recognition or folding
process, has many biological implications (Weinreb et al. 1996; Wright and Dyson
1999; Uversky, Oldfield, and Dunker 2005; Chiti and Dobson 2006; Herczenik and
Gebbink 2008).
We can probe the thermodynamics of the transitions of proteins in folding and
recognition via several thermodynamic variables and their fluctuating conjugates
including temperature, pressure, or concentration, especially of cosolvents. A spe-
cific class of cosolvents known as
osmolytes
are a particularly interesting biologi-
cal perspective because of their evolutionarily selected use to regulate cell volume
and stabilize proteins against environmental osmotic stress conditions to which cells
309
