Comparison based on statistical thermodynamics between globule-to-coil transition of poly(N-isopropylacrylamide) and cold denaturation of a protein

Abstract When the temperature T becomes sufficiently low, poly(N-isopropylacrylamide) (PNIPAM) and a protein, respectively, cause the globule-to-coil transition and the cold denaturation (i.e., transitions to states comprising more extended structures). It is experimentally known for PNIPAM that the coil state is soluble in water but the globule state is insoluble. By contrast, both of the cold-denatured and native states of a protein are soluble. Using our recently developed statistical-mechanical theory combined with molecular models for water, we show that the two structural transitions share physically the same mechanism but still the difference between PNIPAM and a protein in terms of the solubilities of the two states can be reproduced. The solute hydration can be decomposed into the two processes: the creation of a cavity matching the solute structure at the atomic level in water (process 1: hydrophobic hydration); and the incorporation of solute–water van der Waals interaction potential followed by that of solute–water electrostatic interaction potential (process 2). The hydration free energies, energies, and entropies in processes 1 and 2 are denoted by μH,1 > 0 and μH,2  > 0 at high T for PNIPAM but μH(Denatured)