The present study shows on the basis of the thermodynamic stability criteri
on (partial derivative S/partial derivative T)(p) > 0 that partitioning of
the entropy of cold-unfolding of a protein into independent positive confor
mational and negative hydrational contributions is incorrect. Furthermore i
t provides a new microscopic interpretation of protein heat capacity that t
akes into account the significant fluctuations in energy and entropy which
result from the small size of these macromolecules. (C) 1999 Elsevier Scien
ce B.V. All rights reserved.