Hydrophobic Collapse of Long Alkane Chains in Water and Water/Ethanol Mixtures

Protein folding is of tremendous importance in biology, but the mechanism of folding is still not well-understood. Various non-biopolymers in “good” solvents have been studied extensively to mimic such dramatic collapse of chain conformations, and the behavior has been explained in terms of hydrogen bonding and preferential adsorption. But little attention has been paid to the role of hydrophobic effect in such cases. To unravel the importance of hydrophobicity, here, we choose three long alkane chains (C20, C30, C40) as our model systems. A single chain in water, and water/ethanol mixtures is simulated using all-atom replica exchange molecular dynamics technique at temperatures (Ts) between 274 K and 366 K. In pure water, at all Ts, we see a two-state-like behavior in the radius of gyrations (R_g) of the chain conformations with the chain arranging into either a coil (larger R_g) or a globule (smaller R_g). The relative fractions of two populations, f_C and, f_G are quantified using 2D probability densities of chain conformations constructed with R_g and number of native contacts as two variables. We find that f_G systematically increases with T for the chosen alkanes. Further, C20 remains mostly extended and C40 mostly collapsed at all Ts while C30 shows a crossover between f_C and f_G at an intermediate T. We estimate the free energy of such transitions based on f_C and f_G and explain the collapse behavior in terms of enthalpic and entropic components of the free energy. On addition of small amount of ethanol in water, we find that chain conformations are more collapsed compared to the pure water case, showing a signature of cononsolvency. At this composition, ethanol is found to be preferentially adsorbed near the chain, aligned with literature. In the pure ethanol case, however, chains swell and adopt more extended conformations. These observations could provide insights to the role of hydrophobicity in polymer collapse and protein folding.