Water around hydrophobic groups

As mentioned earlier, proteins are subject to cold denaturation because they exhibit maximal stability at temperatures greater than 0°C. The basis of this effect is the reduction in the stabilizing influence of hydrophobic interactions as temperature is reduced. Recall that the burial of hydrophobic side-chains in the folded protein is favored by entropy considerations (AS is positive), but that the enthalpy change associated with these burials is unfavorable (AH, too, is positive). Thus, as temperature decreases, there is less energy available to remove water from around hydrophobic groups in contact with the solvent. Furthermore, as temperature is reduced, the term [— TAS] takes on a smaller absolute value. For these reasons, the contribution of the hydrophobic effect to the net free energy of stabilization of a protein is reduced at low temperatures, and cold-induced unfolding of proteins (cold denaturation) may occur. 

Rezus YLA, Bakker HI. Observation of immobilized water molecules around hydrophobic groups. Phys. Rev. Lett. 2007 99 ... 

In general, incorporation of hydrophobic groups into PIPAAm chains decreases the LCST [29-31]. Hydrophobic groups alter the hydrophilic/ hydrophobic balance in PIPAAm, promoting a PIPAAm phase transition at the LCST, water clusters around the hydrophobic segments are excluded from the hydrophobicaUy aggregated inner core. The resulting isolated hydrophobic micellar core does not directly interfere with outer shell PIPAAm chain dynamics in aqueous media. The PIPAAm chains of the micellar outer shell therefore remain as mobile linear chains in this core-shell micellar structure. As a result, the thermoresponsive properties of PIPAAm in the outer PIPAAm chains of this structure are unaltered [23-27,32]. 

Since AG° = AH0- TAS° (see Chapter 6), it follows that the negative value of AG° for hydrophobic interactions must result from a positive entropy change, which may arise from the restricted mobility of water molecules that surround dissolved hydrophobic groups. When two hydrophobic groups come together to form a "hydrophobic bond," water molecules are freed from the structured region around the hydrophobic surfaces and the entropy increases. The AS° for Eq. 2-9 is about 12 J deg 1 mol-1. Attempts have been made to relate this value directly to the increased number of orientations possible for a water molecule when it is freed from the structured region.64 However, interpretation of the hydrophobic effect is complex and controversial.65-713... 

The water molecules that are in immediate contact with dissolved nonpolar groups are partially oriented. They form a cagelike structure around each hydrophobic group. When particles surrounded by such hydration layers are 1-2 nm apart, they sometimes experience either a fairly strong repulsion or an enhanced attraction caused by these hydration layers.21 64 66,72 Direct experimental measurements have shown that these effects extend to distances of 10 nm21,63 and can account for the previously mentioned long-range van der Waals forces. 

When hydrophobic side-chains of amino acids are in contact with water, they can only be accommodated in the aqueous phase if water structure is altered. Water near nonpolar groups forms what are sometimes referred to as cages or clathrates around these groups. Water molecules in these cages possess a relatively high amount of structure compared to the bulk water of the solution. It should be clear, then, why an increase in the entropy of the sys-... 

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