22 INFLUENCE OF TEMPERATURE ON BIOLOGICAL SYSTEMS 



would contain more of the native type of folding. The relative amounts 

 of the two forms would presumably vary as the temperature, the solvent 

 and the extent of intramolecular cross-linking were varied. 



It should be strongly emphasized that this attractive hypothesis must 

 be used with a great deal of caution. The polypeptide chain of proteins, 

 with the wide variety of side chains that it has dangling from it, may very 

 well be able to fold in states other than the two that have been postulated 

 above. Optical rotatory power provides us with but a single number. 

 Useful though this number may be in characterizing the state of the mole- 

 cule, it could easily lead to a serious oversimplification of our interpreta- 

 tion of the changes in protein structure that occur on denaturation under 

 different conditions. One shudders to think of the oversights that would 

 be possible if, for instance, two completely different states of folding hap- 

 pened to have the same optical rotation. 



; SUMMARY 



One of the principal factors determining the behavior of living organisms 

 at high temperatures is the stability of their proteins, and any discussion 

 of the effects of temperature on protein stability will usually invoke the 

 word 'denaturation.' This word has long been used to describe the loss of 

 activity and solubility that results from exposure to high temperature, 

 but more recently it has been defined in more fundamental terms, in- 

 volving reversible and irreversible structural changes peculiar to proteins. 

 Both meanings of the word are useful, but confusion has resulted when the 

 existence of two meanings has not been recognized. 



Two complementary types of experimental measurement are avail- 

 able for detecting the structural changes that accompany protein de- 

 naturation. One type of property is sensitive to the over-all shape of the 

 molecule and is illustrated by the solution viscosity, the rotational dif- 

 fusion rate and dissymmetry in the scattering of light. The other type 

 of property is determined by short-range interactions between different 

 parts of the molecule and is illustrated by infra-red and ultra-violet 

 spectra, optical rotatory power and the chemical reactivity of groups in 

 the molecule. 



Studies of the structural changes that occur in proteins during denatura- 

 tion should, if possible, be made using at least one property from each 

 of the two types in order to give a maximum amount of structural informa- 

 tion with a given amount of experimental effort. The viscosity and the 

 optical rotatory power are especially convenient for this purpose. Struc- 

 tural changes that lead to a change in viscosity arc usually interpreted in 

 terms of a model consisting of a rigid ellipsoid, but the random coil model 

 is more suitable for some conditions and it is not hydrodvnamically 



