A protein’s stability depends on the hydrophobic interactions between amino acid side chains within its folded structure and the arrangement of water molecules around it which make up the solvation layer.
Proteins largely function in an aqueous environment, so hydrophobic interactions are important to impart stability in the tertiary structure of a folded protein. Amino acids with non-polar, hydrophobic R groups cluster together on the inside of the protein (away from water), leaving hydrophilic amino acids on the outside to interact with surrounding water molecules.
A folded protein has an overall lower entropy relative to the unfolded form. This is balanced out by the increase of entropy that comes from the surrounding water molecules (solvation layer) upon protein folding. Hydrophobic interactions on the outer surface of the folded protein would decrease the possible conformations of water molecules, so by containing the hydrophobic R groups in the internal folds of the protein, the entropy of the solvation layer is increased. This balances out the loss of entropy from folding the protein.
Protein folding and therefore stability is driven primarily by entropy.
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• Hydrophobic interactions and the increase of entropy in the solvation layer is important for a folded protein’s stability.
tertiary structure: the overall 3D structure of a polypeptide, which results from folding of the peptide chains to allow for interactions between the R group side chains and increases the overall stability.
hydrophobic interactions: amino acids with nonpolar, hydrophobic R groups cluster together on the inside of the protein, leaving hydrophilic amino acids on the outside to interact with surrounding water molecules.
solvation layer: water molecules around the protein; the containment of hydrophobic amino acids away from the aqueous media increases the entropy of the solvation layer.