Chemistry Reference
In-Depth Information
11
Why Is Fluctuation
Solution Theory
Indispensable for the
Study of Biomolecules?
Seishi Shimizu
CONTENTS
11.1 Introduction and Scope ................................................................................. 288
11.2 Why Is Fluctuation Solution Theory Indispensable? .................................... 288
11.3 Protein Hydration and Its Microscopic Meaning ......................................... 293
11.3.1 Molecular Crowding: The Dominance of Osmolyte Exclusion in
Osmotic Stress .................................................................................. 293
11.3.2 Relationship to the Volumetric Analysis .......................................... 296
11.3.3 Summary .......................................................................................... 296
11.4 Cosolvent-Induced Denaturation and Stabilization ...................................... 296
11.4.1 Hypotheses Concerning the Origin of Cosolvent Denaturation ....... 296
11.4.2
m
-Value Analysis and the Fluctuation Solution Theory ................... 297
11.5 Cosolvent-Induced Modulation of Thermal Denaturation ........................... 299
11.6 Protein-Water and Protein-Cosolvent Interactions ..................................... 301
11.6.1 Theory ............................................................................................... 301
11.6.2 Urea and Trehalose ........................................................................... 302
11.6.3 Molecular Crowding .........................................................................304
11.6.4 The Hofmeister Effect ...................................................................... 305
11.7 Conclusions ................................................................................................... 306
Abstract
: How does urea denature proteins, whereas sugars, polyols, and
crowders stabilize proteins? This question had been answered by the use of
simple thermodynamic models assuming competitive solvent binding on pro-
tein surfaces. Yet the treatment of solvation in the language of stoichiometric
binding has caused a number of difficulties and controversies. On the contrary,
fluctuation theory has not only cleared up such confusions, but also has pro-
vided a unifying picture of the cosolvent effect, spanning from urea denatur-
ation, through crowding, to the Hofmeister series.
287
