Protein folding and stability

Lesson 9 : Proteins – Classification, Functions, Structure - Amino Acids

Protein folding and stability

Once a polypeptide is made, it then folds into its characteristic three-dimensional shape.

Protein folding and stabilization depend upon noncovalent forces, including the hydrophobic effect, hydrogen bonding, van der Waals interactions, and charge-charge interactions.

Although individually weak, collectively they are strong. The weakness gives the protein flexibility to change conformations. Once in place, the collective effect keeps the protein in its proper shape.

It appears that hydrophobic effects are very important initially, such that the protein “collapses” onto itself. Then some parts of secondary structure begin to form.

The Hydrophobic Effect

  • Proteins are more stable when their hydrophobic R-groups are in the interior of a protein and away from water.
  • Nonpolar side chains then interact with each other.
  • Polar side chains remain in contact with water on the protein surface.

Hydrogen Bonding

  • Hydrogen bonds in ? helices, ? sheets and turns form first as a protein folds àinto defined regions of secondary structure.
  • Many hydrogen bonds ultimately form between the polypeptide backbone and water, between backbone and R-groups, between R-groups, and between R-groups and water.
  • Those hydrogen bonds within interior of protein are more stable than those on the surface because these bonds do not then compete with water molecules.

Van der Waals Interactions and Charge-Charge Interactions

Van der Waals contacts between nonpolar side chains are also important for protein stability.

Charge-charge interactions contribute minimally to protein stability because most ionic bonds are found on the surface of a protein.


  • Protein folding does not involve a random search for the proper conformation.
  • Secondly, the final shape of a protein is dependent upon its primary structure.
  • Small proteins can fold properly in vitro, but larger ones need the help of molecular chaperones.
  • Chaperones are proteins that assist with protein folding by binding to proteins before they are completely folded.
  • They prevent the formation of incorrectly folded intermediates that may trap a polypeptide into an improper form.
  • They also bind to protein subunits and prevent them from aggregating and precipitating
Last modified: Wednesday, 18 January 2012, 11:07 AM