Relationship of protein thermostability to accessible surface area

Abstract

THE pH of an unbuffered protein solution subjected to a continuous temperature increase usually exhibits a single inflection point associated with the cooperative thermal denaturation of the native protein structure¹. Bull and Breese² have used this procedure to demonstrate that the midpoints (T_m) for the thermal denaturation of 14 proteins correlate with the average residue volumes of their constituent amino acid residues and have proposed that this parameter is the principal determinant of protein thermostability. We report here our study of their proposal by extension of these measurements to include 20 additional well characterised proteins, selected because of their availability in homogeneous form. With this expanded data base, solvent-accessible surface area was found to result in a better correlation with protein thermostability.