The 20 Amino Acids: Hydrophobic, Hydrophilic, Polar and Charged Amino Acids and their Function in Protein Structures

Amino acids are put together into a polypeptide chain on the ribosome in a process called protein synthesis, or translation. During this process the polypeptide bond, the covalent bond between two amino acid residues, is formed. There are 20 amino acids most commonly occurring in nature. Each of them has its special properties, which are defined by the type of the side chain they possess. It is the side chain which makes each of the 20 amino acids unique and provides it with a role to play in protein structure. Depending on the particular properties of the amino acid residue, for example its propensity to be in contact with a polar solvent like water, it is classified into one of the following classes: hydrophobic, polar or charged. The charged amino acid residues include lysine (+), arginine (+), aspartate (-) and glutamate (-). Polar amino acids include serine, threonine, asparagine, glutamine, histidine and tyrosine. The hydrophobic amino acids include alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophane, cysteine and methionine, The amino acid glycine does not have a side chain and is hard to assign to a certain class. However, glycine is often found on the surface of the protein tertiary structure in loop regions and provides additional flexibility to these regions. In contrast, proline provides rigidity to the protein structure, by imposing certain torsion angles on the segment of the polypeptide chain where it is located. Together with proline, glycine is often highly conserved within a certain protein family. The reason is that the special properties of these two amino acids distinct them from other amino acids and are important for preserving the type of the protein tertiary structure within a protein family. We will come back to this question later when we will discuss torsion angles and the Ramachandra plot.

Below the 2o most common amino acids in proteins are listed with their three-letter and one-letter codes:

The Twenty Amino Acids Most Common in Proteins:


Charged:
• Arginine - Arg - R
• Lysine - Lys - K
• Aspartic acid - Asp - D
• Glutamic acid - Glu - E

Polar (may participate in hydrogen bonds):
• Glutamine - Gln - Q
• Asparagine - Asn - N
• Histidine - His - H
• Serine - Ser - S
• Threonine - Thr - T
• Tyrosine - Tyr - Y
• Cysteine - Cys - C
• Methionine - Met - M
• Tryptophan - Trp - W

Hydrophobic (normally buried inside the protein core):
• Alanine - Ala - A
• Isoleucine - Ile - I
• Leucine - Leu - L
• Phenylalanine - Phe - F
• Valine - Val - V
• Proline - Pro - P
• Glycine - Gly - G

The figure below shows the distribution of the 20 amino acid residues within the protein tertiary structure:
Distribution of amino acids in a protein structure
The graph above nicely demonstrates the location of the 20 amino acids in different regions of a protein tertiary structure. The vertical axis shows the fraction of highly buried within the protein core (inaccessible for water) amino acid residues, while the horizontal axis shows the amino acid names in one-letter code. Apparently there is very small fraction of buried charged residues, while in the case of the non-polar amino acids the fraction is very high.
Taken from the tutorial by J.E. Wampler,
The propensity of amino acid residues to be (or not to be) in contact with polar solvent largely controls the distribution of each of the 20 amino acids within the volume of a protein structure. Thus, most protein molecules have a hydrophobic core, which is not accessible to solvent and is built up by hydrophobic amino acids. On the other hand, polar and charged amino acids preferentially cover the surface of the molecule and are in contact with the solvent. Very often they also interact with each other: positively and negatively charged amino acids form so called salt bridges between each other, while polar amino acid side chains get involved in hydrogen bonding with side chains or main chain atoms and with water. Since these interactions are crucial for the stabilization of the protein tertiary structure, they are normally conserved within a protein family. A detailed atlas of hydrogen bonding for all 20 amino acids in protein structures was compiled by Ian McDonald and Janet Thornton and can be found here.

In the next chapter we will go through the next level of protein structure hierarchy: the secondary structure.