• Side-chain Ionization and The pI

2.2.4. Classification of Amino Acids

Amino acids are generally divided into groups on the basis of their side chains (R groups).  The most helpful start-point is to separate amino acids into:

2.2.4.A. Amino Acids with Nonpolar Neutral (Uncharged, Hydrophobic) Side Chain:

• Only carbon and hydrogen in their side chains.
• Generally unreactive but hydrophobic.
• Determining the 3-D structure of proteins (they  tend  to cluster on the inside of the molecule). 
• The simplest amino acid is Glycine, which has a single hydrogen atom as its side chain. 
• Alanine, Valine, Leucine and Isoleucine have saturated hydrocarbon R groups (i.e. they only have hydrogen and carbon linked by single covalent bonds).  Leucine and Isoleucine are isomers of each other.
• The side chain of Methionine includes a sulfur atom but remains hydrophobic in nature. 
• Phenylalanine is Alanine with an extra benzene (sometimes called a Phenyl) group on the end.  Phenylalanine is highly hydrophobic and is found buried within globular proteins. 
• Tryptophan is highly hydrophobic and tends to be found immersed inside globular proteins. Structurally related to Alanine, but with a two ring (bicyclic) indole group added in place of the single aromatic ring found in Phenylalanine. The presence of the nitrogen group makes Tryptophan a little less hydrophobic than Phenylalanine.
• Proline is unique amongst the amino acids – its side chain is bonded to the backbone nitrogen as well as to the a-carbon.  Because of this proline is technically an imino rather than an amino acid. The ring is not reactive, but it does restrict the geometry of the backbone chain in any protein where it is present.

Figure 2.7: Structures of amino acids with uncharged hydrophobic side chain.