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

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 μ H,1 > 0 and μ H,2 < 0, ε VH,1 < 0 and ε VH,2 < 0, and S VH,1 < 0 and S VH,2 < 0, respectively. We find that the excluded-volume (EV) terms in ε VH,1 and S VH,1 are strongly dependent on T , whereas not only the sum of the water-accessible surface terms in ε VH,1 and S VH,1 but also ε VH,2 and S VH,2 remain essentially constant against a change in T. The EV term of S VH,1 becomes significantly smaller at low T , which is interpretable as the weakening of the hydrophobic effect and the trigger of the two structural transitions. The changes in structure and properties of water near PNIPAM or a protein upon the transition to a state comprising more extended structures are unimportant. Though μ H,1 is a largely increasing function of T , | μ H,2 | is only very weakly dependent on T. μ H,1 /| μ H,2 | for PNIPAM is much larger than that for a protein, which is attributable to the lower electrostatic affinity of PNIPAM for water. As a consequence, μ H (Coil) < 0 at low T but μ H (Globule) ≫ 0 at high T for PNIPAM but μ H (Denatured) ≪ 0 at low T and μ H (Native) ≪ 0 at high T for a protein (μ H = μ H,1 + μ H,2). Unlabelled Image • PNIPAM exhibits the globule-to-coil transition upon temperature lowering. • The coil state is soluble in water but the globule state is insoluble. • A protein is denatured upon temperature lowering (cold denaturation). • Both of the cold-denatured and native states are soluble. • All of these facts can be elucidated by our statistical-mechanical theory. [ABSTRACT FROM AUTHOR]