THE HEAT-CAPACITY OF PROTEINS

The heat capacity plays a major role in the determination of the energ etics of protein folding and molecular recognition. As such, a better understanding of this thermodynamic parameter and its structural origi n will provide new insights for the development of better molecular de sign strategies. In this paper we have analyzed the absolute heat capa city of proteins in different conformations. The results of these stud ies indicate that three major terms account for the absolute heat capa city of a protein: (1) one term that depends only on the primary or co valent structure of a protein and contains contributions from vibratio nal frequencies arising from the stretching and bending modes of each valence bond and internal rotations; (2) a term that contains the cont ributions of noncovalent interactions arising from secondary and terti ary structure; and (3) a term that contains the contributions of hydra tion. For a typical globular protein in solution the bulk of the heat capacity at 25 degrees C is given by the covalent structure term (clos e to 85% of the total). The hydration term contributes about 15 and 40 % to the total heat capacity of the native and unfolded states, respec tively. The contribution of non-covalent structure to the total heat c apacity of the native state is positive but very small and does not am ount to more than 3% at 25 degrees C. The change in heat capacity upon unfolding is primarily given by the increase in the hydration term (a bout 95%) and to a much lesser extent by the loss of noncovalent inter actions (up to similar to 5%). It is demonstrated that a single univer sal mathematical function can be used to represent the partial molar h eat capacity of the native and unfolded states of proteins in solution . This function can be experimentally written in terms of the molecula r weight, the polar and apolar solvent accessible surface areas, and t he total area buried from the solvent. This unique function accurately predicts the different magnitude and temperature dependences of the h eat capacity of both the native and unfolded states, and therefore of the heat capacity changes associated with folding/unfolding transition s. (C) 1995 Wiley-Liss, Inc.