The linear polypeptide chain folds in a particular arrangement, resulting in a three-dimensional structure. Proteins unfolded in vitro fold back to their original ("native") state when solution conditions are returned to those in which the folded protein exists. All the information for the native fold appears therefore to be contained within the primary structure: proteins are self-folding.

The 3D structure is stabilized by a multitude of specific interactions between the various chemical groups present. If the differences between two homologous species are examined, a general tendency is observed for chemically similar amino acid residues to be found at the same position. For example, the substitution of one acidic residue, e.g. Glu for Asp, is likely to be of less consequence to the interactions with nearby residues than would the substitution of Glu for the hydrophobic residue Val.

The reason that this field is so important is that the structure of a proteins is intrinsically related to its function. Experimental structure determination or structure prediction aids the elucidation of protein function; conversely, synthetic protein sequences might be designed so that the protein performs a desired function.

The study of protein structure is therefore not only of fundamental scientific interest in terms of understanding biochemical processes, but also produces very valuable practical benefits.

In this section, we will briefly introduce different methods for predicting secondary and tertiary structures.