Fibrous proteins may respond to stretching by changing their conformation .

Small changes in pH can add or remove H⁺ ions from side chain groups on the surface of a protein, without causing any permanent damage to the conformation. At a certain pH, called the isoelectric point, the protein molecule will have no overall ionic charge and so will have its minimum solubility in water. Different proteins have different isoelectric points. Chemists can use this to precipitate one protein from a mixture of proteins in solution by adjusting the pH to the isoelectric point of that protein.

Urea (NH₂CONH₂) is one of several small molecules which, at high concentrations, can weaken the non-covalent forces keeping the secondary and tertiary structure intact. The protein becomes denatured as its structure unravels and produces separate random coils in solution. The protein in this state has none of its original biological properties. If the urea is removed, denaturation may be reversed as the protein can slowly coil and fold back into its original conformation, regaining all its biological properties. However, this process may be difficult for proteins with many disulphide bridges .

When biochemists are investigating a protein that has been extracted from an organism, and so removed from its ‘natural’ environment, they have to make sure they do not damage it permanently. Permanent damage is irreversible denaturation and happens when the secondary and tertiary structure are unravelled leaving peptide chains to tangle with each other and precipitate out of solution. Temperatures above about 50¡C and pH values outside the range 3-9 are often enough to bring this about. When you boil an egg the proteins in the white denature forming an insoluble mass and do not turn back into their original liquid state.

Organisms can produce abnormal protein by mutation (see Section 4.3). About one in three hundred northern Europeans produce abnormal haemoglobin molecules. Abnormal haemoglobins are more common in some races, e.g. black Africans. These usually differ from normal haemoglobin by one a-amino acid change. Almost all of the changes to a-amino acids at the surface of the molecule are harmless, but putting a val in place of a glu at the sixth position of one of the sub-units produces haemoglobin S. People who make only haemoglobin S suffer from sickle cell anaemia. At low oxygen levels the abnormal haemoglobin molecules collect together in the red blood cells and form extended crystals that distort the cell into a sickle (crescent) shape (Figure 14). These cells tend to cause blockages in small blood vessels.

Protein chemists have been investigating ways of modifying proteins by deliberately altering the primary structure . You can read about this protein engineering in Section 4.3.