Effects of lengthscales and attractions on the collapse of hydrophobic polymers in water

Abstract

We present results from extensive molecular dynamics simulations of collapse transitions of hydrophobic polymers in explicit water focused on understanding effects of lengthscale of the hydrophobic surface and of attractive interactions on folding. Hydrophobic polymers display parabolic, protein-like, temperature-dependent free energy of unfolding. Folded states of small attractive polymers are marginally stable at 300 K and can be unfolded by heating or cooling. Increasing the lengthscale or decreasing the polymerwater attractions stabilizes folded states significantly, the former dominated by the hydration contribution. That hydration contribution can be described by the surface tension model, ⌬G ‫؍‬ ␥(T)⌬A, where the surface tension, ␥, is lengthscale-dependent and decreases monotonically with temperature. The resulting variation of the hydration entropy with polymer lengthscale is consistent with theoretical predictions of Huang and Chandler [Huang DM, Chandler D (2000) Proc Natl Acad Sci USA 97:8324 -8327] that explain the blurring of entropy convergence observed in protein folding thermodynamics. Analysis of water structure shows that the polymer-water hydrophobic interface is soft and weakly dewetted, and is characterized by enhanced interfacial density fluctuations. Formation of this interface, which induces polymer folding, is strongly opposed by enthalpy and favored by entropy, similar to the vapor-liquid interface.dewetting ͉ folding ͉ hydration entropy ͉ hydrophobic hydration ͉ hydrophobic interaction H ydrophobic interactions are one of the major contributors to biological self-assembly in solution, including protein folding and aggregation, micelle and membrane formation, and biomolecular recognition (1-5). Recent work in this area has focused on the lengthscale dependencies of hydrophobic hydration and interactions (4,(6)(7)(8)(9). In particular, a recent theory by Lum, Chandler, and Weeks (6) highlighted the different physical mechanisms of solvation of small and large hydrophobic solutes in water. Small solutes are accommodated in water through molecular-scale density fluctuations (10, 11), whereas solvation of larger solutes requires formation of an interface similar to that between a liquid and a vapor (4,6,12). This change in physics is also reflected in thermodynamic (entropy vs. enthalpy dominated hydration) (9) and structural (wetting vs. dewetting of the solute surface) (4, 12, 13) aspects of hydration. Similarly, interactions between larger hydrophobic solutes in water (14-18) are characteristically distinct from those between their molecular counterparts (19,20).The differences between the hydration and interactions of small and large solutes characterize many-body effects in hydrophobic phenomena. Effects of similar origin are also at work in association of small hydrophobic solutes into a larger aggregate (21,22) and are quantified by the n-particle potential of mean force (PMF) (23-26). For n Ͼ 3, however, the dimensionality of the system makes calculations of n-particle PMFs computa...

Signature of hydrophobic hydration in a single polymer

“…The temperature and monomer size dependence of ΔG hyd are consistent with hydrophobic polymer unfolding simulations from Athawale et al (27). Their work suggests that the turnover behavior of ΔG hyd is present only when a Lennard-Jones attraction between polymer and water is introduced.…”

“…Furthermore, it was pointed out that the turnover temperature is much more sensitive to the size of the solute than the attraction between solute and solvent (28). The length of the polymer used in the experiment reported here is much greater (hundreds of nanometers) than the 25 mer (∼4 nm) used in the simulation from Athawale et al (27). As a result, the experiment does not probe the finite size effect as in the work of Athawale et al In addition, because both area and volume of the extended polymer are proportional to the extended chain length, the experiment cannot directly test whether the extended polymer ΔG hyd is area or volume dependent.…”

“…However, it was argued that the correction to the effective surface tension to maintain the correlation between ΔG hyd and SASA at small length scales lacked a clear physical meaning (16). Instead of depending on a scaling relation with SASA, theories and simulations were developed predicting that ΔG hyd has nontrivial size dependence: Below approximately 1 nm radius, ΔG hyd of a spherical solute scales roughly with the solute volume; whereas above this value, ΔG hyd scales with SASA and asymptotically approaches the behavior described by macroscopic interfacial thermodynamics (6,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). These treatments correctly predict the trend for the temperature dependence of ΔG hyd for small molecules.…”

An improved coarse-grained model of solvation and the hydrophobic effect

“…Numerous studies a) Electronic mail: chandler@berkeley.edu. of hydrophobicity 4,14,[23][24][25][26][27][28][29][30][31][32][33] have shown that rare solvent motions and dewetting transitions in confining environments play a critical role in solute assembly and function. Our model adequately captures these rare and important fluctuations.…”

Static and dynamic correlations in water at hydrophobic interfaces

“…Examples of drying-induced phenomena include the hydrophobic collapse of a polymer chain (25)(26)(27), dewetting-induced attractive interactions studied in detail by Berne, Zhou, and coworkers in the collapse of multidomain proteins and hydrophobic particles (28)(29)(30), and large hydrodynamic slip lengths at the solid-water interface (31)(32)(33).…”