DNA encodes twenty types of amino acids that make up proteins in all organisms, from bacteria to plants, to animals. These amino acids can be broadly grouped based on their biophysical properties (e.g., charge, hydrophobicity, and polarity of their side chain). The properties of the side chains govern the way they interact with surrounding molecules, and consequently impact the protein’s 3D structure.
Non-polar Amino Acids
Non-polar amino acids carry a hydrophobic side chain, and are commonly located in the interior of proteins, whereas polar amino acids are typically found on protein surfaces due to the hydrophilic properties of their side chains.
Polar and Electrically-charged Amino Acids
Among the 20 amino acids, five have a side chain that can be electrically charged at physiological pH. Two are negatively charged (acidic) and three are positive (basic). These charged amino acids play important roles in stabilizing protein 3D structures, and mediating protein-ligand interactions via electrostatic attractions.
Special Amino Acids
Nonetheless, there are three amino acids that stand out for their unique properties: (1) Glycine is the simplest amino acid and it doesn’t really have a side chain. It has a hydrogen as its R group giving glycine much flexibility to fit in different parts of proteins. (2) Cysteine has a reactive sulfur-containing thiol group that can form disulfide bonds between two cysteine residues. (3) Proline incorporates the backbone into its side chain to form a cyclic ring, making it unable to adopt many of the main chain conformations. It can also introduce kinks to occur in a protein chain.
Non-standard Amino Acids
Besides the 20 standard amino acids, many non-standard amino acids are also found in cells, which are typically chemically modified after they are incorporated into a protein. These chemical modifications are part of post-translational modifications. Examples of these non-standard amino acids include carboxyglutamic acid (a product of glutamine carboxylation), hydroxyproline (a product of proline hydroxylation), methyllysine (a derivative of lysine where its side chain has been methylated) and more. These modifications result in important protein properties that enable and improve a wide range of biological functions.