3] CONFIGURATION OF GLOBULAR PROTEINS 37 



sedimentation and diffusion coefficients than molecules of the same mole- 

 cular weight which are random coils or rigid rods. To distinguish between 

 random coils and rigid rods is equally easy if the macromolecule under con- 

 sideration can be prepared with a range of molecular weights. The radius 

 of gyration, for example, would then be proportional to the molecular weight 

 for rods and roughly to the square root of the molecular weight for random 

 coils. For naturally-occurring substances of fixed molecular weight the dis- 

 tinction between rods and random coils generally requires more subtle ana- 

 lysis. The present paper is concerned only with macromolecules bearing 

 electric charges. It will appear subsequently that such charges have a con- 

 siderable effect on the configuration of randomly-coiled molecules, enabling 

 us to distinguish them readily from rigid rods. 



The simplest physical measurement which will distinguish between the 

 extreme configurations here under discussion is the intrinsic viscosity, [r]]. 

 For rigid spheres of unit density [17] =2-5 cc./gram, independent of mole- 

 cular weight. For rigid rods or random coils, [q] is much larger: it varies 

 roughly as M^ for the former and as M°-^'^° for the latter (where M = 

 mol. wt.). 



It would be naive, of course, to expect all macromolecules to fall into 

 one of the extreme configuration classes just discussed. Intermediate con- 

 figurations which undoubtedly exist are helical rods with a small number 

 of breaks, random coils with some cross-links, compact spherical regions 

 joined by short lengths of randomly-coiled chain, etc. To distinguish these 

 from one another in an unequivocal way is at present not possible. 



ISOELECTRIC GLOBULAR PROTEINS 

 IN AQUEOUS SOLUTION 



It is clear from the preceding discussion that the configuration of macro- 

 molecules in solution is determined by the properties of the solvent as much 

 as by those of the macromolecules. Thus, the configuration of a protein 

 molecule is likely to differ from one solvent to another, and in any solvent 

 may differ from the configuration in the crystalHne state. This paper will 

 concern itself with the configuration of common globular proteins in dilute 

 aqueous solution. The conclusions reached will not apply to crystalline pro- 

 teins or to proteins in other solvents. Indeed, it is well-established that con- 

 figurations of proteins in solvents such as concentrated aqueous urea differ 

 markedly from what they are in water. 



When many of the common globular proteins, in aqueous solution, are 

 examined at or near their isoelectric points, they can usually at once be 

 assigned to a configuration much closer to that of a compact, rigid, im- 

 penetrable sphere than to the other extremes mentioned earher. This is 

 illustrated, for example, by the intrinsic viscosities listed in Table 1. A 

 similar conclusion is reached from all other pertinent measurements. 



It should be noted that three of the proteins listed in Table 1, fibrinogen. 



