METHOD OF DETERMINING RELATIVE STABILITY OF DIFFERENT CONFORMATIONAL STATES OF BIOLOGICAL MACROMOLECULES

A general approach to the determination of relative stability of any pair of con‐formational states of biological macromolecules or their complexes (in particular, to the determination of relative stability of native and disordered states of the macromolecule) has been suggested. For determining the free energy difference of the two states under the conditions when one of them is considerably more advantageous than the other, it is necessary for the macromolecule to be influenced by the transforming agent which levels free energies of both the conformational states, and to determine the external parameter derivative of the free energy difference in the region of the conformational transition induced by the change in this parameter. If the character of the dependence of this derivative on the external parameter (temperature, solvent composition, etc.) is known, then this allows the determination of the free energy difference of the two states under the conditions considered, even including conditions far from the transition region. The value of the derivative of the free energy difference in the transition region in many cases can be measured directly (in particular, when using calorimetry), while in cases when a direct measurement of the derivative is impossible, it can often he estimated experimentally from the steepness of the conformational transition. The methods of this estimation and also a possible character of the change of the considered derivative during variation of the external parameter are considered for the case when the transforming agent is one of the components of the solvent and, consequently, the derivative of the free energy difference is equal to the difference of number of molecules of this component hound with the macromolecule in two conformational states. Copyright © 1969 John Wiley & Sons, Inc.