Entropy calculations on a reversibly folding peptide: Changes in solute free energy cannot explain folding behavior

The configurational entropy of a beta -heptapeptide in solution at four dif ferent temperatures is calculated, The contributions of the backbone and of the side-chain atoms to the total peptide entropy are analyzed separately and the effective contribution to the entropy arising from correlations bet ween these terms determined. The correlation between the backbone and side- chain atoms amounts to about 17% and is rather insensitive to the temperatu re. The correlation of motion within the backbone and within side-chains is much larger and decreases with temperature. As the peptide reversibly fold s at higher temperatures, its change in entropy and enthalpy upon folding i s analyzed. The change in entropy and enthalpy upon folding of the peptide alone cannot account for the observed change in free energy on folding of t he peptide in solution. Enthalpic and entropic contributions of the solvent thus also play a key role. Proteins 2001; 43:45-56. (C) 2001 Wiley Liss, I nc.