2. Secondary structure:

Generally, proteins have a core of hydrophobic residues surrounded by a shell of hydrophilic residues. Since the peptide bonds themselves are polar they are neutralized by hydrogen bonding with each other when in the hydrophobic environment. This gives rise to regions of the polypeptide that form regular 3D structural patterns called 'secondary structure'. There are two main types of secondary structure are the alpha helix and the beta sheet. Each of these two secondary structure elements have a regular geometry, meaning they are constrained to specific values of the dihedral angles ψ and φ. Both the alpha helix and the beta-sheet represent a way of saturating all the hydrogen bond donors and acceptors in the peptide backbone. These secondary structure elements only depend on properties of the polypeptide main chain, explaining why they occur in all proteins. The part of the protein that is not in a regular secondary structure is said to be a "non-regular structure" (not to be mixed with random coil, an unfolded polypeptide chain lacking any fixed three-dimensional structure).

Other helices, such as the 3₁₀ helix and π helix, are calculated to have energetically favorable hydrogen-bonding patterns but are rarely if ever observed in natural proteins except at the ends of α-helices due to unfavorable backbone packing in the center of the helix.

Other extended structures such as the polyproline helix and alpha sheet are rare in native state proteins but are often hypothesized as important protein folding intermediates. Tight turns and loose, flexible loops link the more "regular" secondary structure elements. The random coil is not a true secondary structure, but is the class of conformations that indicate an absence of regular secondary structure.

Amino acids vary in their ability to form the various secondary structure elements. Proline and glycine are sometimes known as "helix breakers" because they disrupt the regularity of the a-helical backbone conformation; however, both have unusual conformational abilities and are commonly found in turns.

Amino acids that prefer to adopt helical conformations in proteins include methionine, alanine, leucine, glutamic and lysine ("MALEK" in amino-acid 1- letter codes); by contrast, the large aromatic residues (tryptophan, tyrosine and phenylalanine) and C _β -branched amino acids (isoleucine, valine, and threonine) prefer to adopt β-strand conformations. However, these preferences are not strong enough to produce a reliable method of predicting secondary structure from sequence alone.

Some simple combinations of secondary structure elements have been found to frequently occur in-protein structure and are referred to as 'super-secondary structure' or motifs. Structure motifs usually consist of just a few elements, e.g. the 'helix-turn-helix' has just three. However, while the spatial sequence of elements is the same in all instances of a motif, they may be encoded in any order within the underlying gene.

Protein structural motifs often include loops of variable length and unspecified structure, which in effect create the "slack" necessary to bring together in space two elements that are not encoded by immediately adjacent DNA sequences in a gene. Even when two genes encode secondary structural elements of a motif in the same order, nevertheless they may specify somewhat different sequences of amino acids. This is true not only because of the complicated relationship between tertiary and primary structure, but also because the size of the motif elements varies from one protein and the next. Examples of motifs in proteins :

• β-hairpin motif: Consists of two adjacent antiparallel β-strands joined by a small loop. It is present in most antiparallel β structures both as an isolated ribbon and as part of more complex β-sheets.
• β-α-β Motif: Frequently used to connect two parallel β-strands. The central α-helix connects the C-termini of the first strand to the N-termini of the second strand, packing its side chains against the β-sheet and therefore shielding the hydrophobic residues of the β-strands from the surface.
• Greek Key: 4 beta strands folded over into a sandwich shape.
• Helix-loop-helix : Consists of alpha helices bound by a looping stretch of amino acids. Important in DNA binding proteins.
• Zinc finger : Two beta strands with an alpha helix end folded over to bind a zinc ion. This motif is seen in transcription factors.