(Logo) Summary of Amino Acid Properties

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You should be aware of how the following properties of amino acids are important in the context of protein structure:

A general principle concerning packing in proteins can be highlighted by likening a folded protein to a three-dimensional jigsaw. The interiors of proteins have a similar packing density to organic solids; this packing is due to complementary van der Waals surfaces coming into contact upon folding of the polypeptide(s), filling up most of the space in the interior. It is the close fitted-packing which confers rigidity to the structure.
Therefore, if a mutation leads to the replacement of a small side chain by a large one, the folded conformation will tend not to be able to accommodate the new residue. On the other hand, cavities in the structure are unfavourable, so replacement of a large side chain by a small side chain will also tend to destabilize the fold (although cavities might be filled by solvent molecules, depending on the nature of the groups lining them). This table gives volumes (cubic Å) and surface areas (square Å) ( Ron Beavis, Protein Chemistry Lab, Skirball Institute)

Asp, Glu (one negative charge), Lys and Arg (one positive) are ionized under most physiological conditions; His is positively charged or neutral depending on its local environment. Refer to the pKa values.
A specific type of interaction is that which occurs between 2 charged groups of opposite sign: these constitute a salt bridge (or 'ion pair'). There is typically 1 ion pair per approximately 30 protein residues. A less specific property concerns the net charge of a protein. Proteins are found to be most stable at or near the isoelectric point (i.e. at which the net charge is zero).

Charged and neutral polar side chains participate in hydrogen bonds, both with each other, with the main chain polar atoms and with solvent.

The aliphatic side chains Ala, Val, Leu and Ile (and Gly) contain no polar atoms, and therefore interact less favourably with water than they do with other apolar groups. A general feature of globular proteins is that such hydrophobic residues are found in the protein interior, while polar residues occur on the surface. In this respect, protein folding may be roughly compared to the formation of lipid micelles in aqueous solution- the chain becomes arranged such that apolar groups are buried, and polar groups exposed. However, bear in mind that such a clear-cut arrangement is not possible for a polypeptide chain. All residues have main polar chain atoms (N and carbonyl O), and the manner in which their hydrogen bonding capacity is satisified within the protein interior is the foundation for higher levels of structure as will be covered later. On the other hand, several charged and neutral polar side chains have significant apolar surface area.
Nevertheless, hydrophobicity is a very important factor in protein stability; indeed the "hydrophobic effect" is believed to play a fundamental role in the spontaneous folding of proteins. This will be covered later in more detail.
Pro is also aliphatic, but has special conformational properties relating to its location in proteins. Not only aliphatic side chains are hydrophobic: although the sulphur-containing Met side chain has a dipole moment, it is also of apolar character. Disulphide bonds formed by Cys residues (see below) also have apolar surface area. The Phe side chain is strongly hydrophobic, even though its delocalized pi-electron system can take part in weak electrostatic interactions. Trp has the largest side chain, most of which has a non-polar surface, despite the polar N atom. In the same way, the Tyr side chain is of partly hydrohobic character.
PPS Consultant Simon Brocklehurst describes Side-chain Packing in Hydrophobic Cores (this also requires some knowledge of higher levels of structure).

The capacity of the delocalized electrons in aromatic side chains to participate in relatively weak electrostatic interactions has been referred to above. However, in the context of proteins, there is a tendency for aromatic side chains to be 'stacked' against amide and amino groups, rather than accepting protons from them in 'hydrogen bonds'.

Conformationally Unusual Side Chains
Steric hindrance, or the lack of it, means that Pro and Gly play special roles in polypeptide conformation; refer to Jon Cooper's material. Steric constraints are covered in more detail in the next section of the course.
A pair of Cys residues can form a disulphide bond (also known as a cystine bridge) by the oxidation of their side chains. This was the subject of a project by Darren Fast (Univ.Wisconsin, USA) during the 1995 VSNS-PPS course.

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Last updated 28th Jan '96