| Abstrakt: |
Despite the emergence of a molecular picture of urea's protein unfolding mechanism in the past few decades, less is known about its action mechanism on protein aggregation. This is especially relevant for understanding the aggregation of amyloid proteins and peptides, implicated in several neurodegenerative diseases. While urea is believed to weaken the hydrophobic effect, a picture consistent with the decrease in the excess chemical potential of sufficiently large alkanes, interactions with protein polar side chains and backbone atoms are also important. Here, we study, through molecular dynamics, the hydration and aggregation of several alkanes and amphiphilic "mutants" of n-dodecane, in an 8M aqueous urea solution, aiming at getting insight into urea's mode of action. A size-dependent crossover temperature is found, above which the hydration of the alkanes is favored in the aqueous urea solution. The hydration of the alkanes is enhanced via entropy, with the enthalpy opposing hydration, consistent with experiments. The reason is that although solute–solvent interactions are favorable, these are overwhelmed by urea–water and urea–urea interactions. In contrast, water–water interactions and entropy are favored by a water depletion around the solute and a reduced water depletion around methane explains its exceptional solubility decrease. Furthermore, we show that while urea favors the hydration of n-dodecane and the amphiphilic mutants, it slightly enhances and reduces, respectively, the aggregation of the alkanes and the amphiphilic mutants. Thus, opposite to the common view, our results show that urea does not necessarily weaken hydrophobic interactions despite solvation being favored. [ABSTRACT FROM AUTHOR] |
