268 



Robert Platzman and James Franck 



is normally re-formed in the same configuration and the structure maintained 

 by the constraints imposed by neighboring bonds ; only if a number of distur- 

 bances overlap will there be a chance that closure of the bonds occurs in im- 

 proper fashion, and that the disorder becomes irreparable. The model makes 

 possible a satisfactory interpretation of thermodynamic and even kinetic data 

 for thermal denaturation of many proteins (12). It immediately suggests that 

 explanation of the great radiation sensitivity of proteins must be sought in a 

 means of communicating energy from a swiftly moving charged particle to the 

 secondary bonds. Direct energy transfer is negligible, for the coupling is too 

 small (6). The process here advanced provides the required mechanism. 

 Although the analysis given above is admittedly crude (a circumstance for which 

 the lack of relevant and important information on protein structure is chiefly 

 responsible) it is certainly not speculative: it is based upon well established 

 physical principles which are, perhaps, unfamiliar in their present implication. 

 The simultaneous cleavage* of approximately ten secondary bonds following 

 charge localization constitutes a violent perturbation of the protein structure, 

 but probably does not suffice to denature most proteins, at least at ordinary 

 temperatures. This conclusion is suggested by an examination of representative 

 data (Table 1) from analysis of thermal-inactivation kinetics, taken from the 



Table I. Critical Number of Hydrogen-Bond Ruptures From 

 Thermal Inactivation Rates 



(based chiefly upon reference (12)). A// j is the enthalpy of activation, in kcal/mole, ASJ is the 

 entropy of activation, in cal/mole deg, and the values of A'' are calculated by: A/^i = A// J/5, 



Ni = ASt/12. 



work of Stearn (12). Stearn proposed a calculation of N, the number of 

 secondary bonds which have been ruptured in the activated complex (i.e. the 

 critical number for disordering of the conformation), by assuming an average 

 energy requirement of 5 kcal/mole (A^^), or, alternatively, an average entropy 

 incre'ase of 12 cal/mole deg {N^. The values of N^ and N^ so calculated from 

 velocities of thermal denaturation are in impressive accord with one another, 



* The simultaneity of secondary-bond cleavage, which plays a decisive role in the mecha- 

 nism here proposed, has not been accorded much attention in radiobiology heretofore. It 

 necessarily underlies much of the thinking about mechanisms in thermal denaturation, at least 

 implicitly, and has been invoked, for example, in connection with a model of chemical de- 

 naturation by Kauzmann (13). 



