Theoretical analysis on thermal stability of a protein focused on the water entropy

We have recently shown that the water entropy is the key quantity in elucidating the folding/unfolding mechanisms for proteins. Here we consider thermal denaturation. The water-entropy gain upon the transition from the random-coil state to the native structure is calculated for some representative proteins by employing the angle-dependent integral equation theory combined with the multipolar water model and the morphometric approach. It is found that the water-entropy gain at 25 °C divided by the number of residues is a good measure of the thermal stability. A protein with a larger value of this measure tends to have a higher denaturation temperature.