Low-temperature and high-pressure induced swelling of a hydrophobic polymer-chain in aqueous solution

Abstract

We report molecular dynamics simulations of a hydrophobic polymer-chain in aqueous solution between 260 K and 420 K at pressures of 1 bar, 3000 bar, and 4500 bar. The simulations reveal a hydrophobically collapsed state at low pressures and high temperatures. At 3000 bar and about 260 K and at 4500 bar and about 260 K, however, a transition to a swelled state is observed. The transition is driven by a smaller volume and a remarkably strong lower enthalpy of the swelled state, indicating a steep positive slope of the corresponding transition line. The swelling is stabilized almost completely by the energetically favorable state of water in the polymers hydrophobic first hydration shell at low temperatures. Although surprising, this finding is consistent with the observation of a positive heat capacity of hydrophobic solvation. Moreover, the slope and location of the observed swelling transition for the collapsed hydrophobic chain coincides remarkably well with the cold denaturation transition of proteins.

Microscopic Mechanism for Cold Denaturation

“…One class of such models [7,9] associates the phenomena with the different energetic states of shell water, i.e., water molecules neighboring the protein, in a lattice. A more realistic water model [8] supports this view, as water-water hydrogen bonding among shell water has been found to increase at low temperatures and to correlate with cold denaturation. Meanwhile, another class of models suggests that the density fluctuations of water are responsible for cold denaturation [11,12].…”

“…Consequently, cold denaturation has been studied using explicit models that take hydrophobicity into account [7][8][9][10]. One class of such models [7,9] associates the phenomena with the different energetic states of shell water, i.e., water molecules neighboring the protein, in a lattice.…”

Contribution of Water to Pressure and Cold Denaturation of Proteins

“…Experimental data show that for many proteins the native folded state is stable in a limited range of temperatures T and pressures P [3][4][5][6][7][8] and that partial folding is T modulated also in "intrinsically disordered proteins" [9]. By hypothesizing that proteins have only two different states, folded (f) and unfolded (u), and that the f⟷u process is reversible at any moment, Hawley proposed a theory [10] that predicts a close stability region (SR) with an elliptic shape in the T-P plane, consistent with the experimental data [11].Cold and P denaturation of proteins have been related to the equilibrium properties of the hydration water [12][13][14][15][16][17][18][19][20][21][22][23]. However, the interpretations of the mechanism are still controversial [8,[24][25][26][27][28][29][30][31][32][33][34][35][36][37].…”

Temperature-dependent solvation modulates the dimensions of disordered proteins

“…The observation of temperature-induced collapse in proteins thus implies the existence of temperature-dependent interactions, presumably with contributions from the hydrophobic effect (29)(30)(31)(32)(33) or, more generally, changes in solvation free energy as a function of temperature. A critical role for the solvent contribution is supported by molecular simulations of unfolded proteins with different water models (22,34), and even simulations of hydrophobic homopolymers (35)(36)(37)(38)(39) and simple heteropolymers (40) in explicit water models exhibit a similar behavior. However, the detailed origin of the temperature-induced compaction has remained elusive.…”