Amino acids

Amino acids are molecules carrying both a carboxyl (-COOH) and an amine (-NH₂) group. Here follows some example:

In the first example, the two functional groups are bound to the same carbon atom (a-amino acid) while in the second example the two groups are bound to two different carbon atoms (gamma-aminoacids)

Amino acids found in proteins are a-amino acids, i.e., they have amino and carboxyl groups bound to the same carbon atom. An exception is proline, which differs from other amino acids in having a secondary amino group. Furthermore its side chain bounds both the amino and carboxylic group forming a pyrrolidinic ring, it is generally referred as a-imino-acid (a very obsolescent term).

Amino acids differ on the nature of R (also indicated as side chain). Only 20 amino acids (see table below) are commonly found in proteins. With the exception of glycine (R = H), the alpha-carbon of all amino acids is asymmetric (i.e., it binds four different groups). Therefore, these amino acids are optically active and they can exist in a form L and in a form D.  Amino acids found in proteins have the L form.

Amino acid	Three / One letter code	Amino acid	Three / One letter code
Alanine	Ala / A	Leucine	Leu / L
Arginine	Arg / R	Lysine	Lys / K
Asparagine	Asn / N	Methionine	Met / M
Aspartic acid	Asp / D	Phenylalanine	Phe / F
Cysteine	Cys / C	Proline	Pro / P
Glutamic acid	Glu / E	Serine	Ser / S
Glutamine	Gln / Q	Threonine	Thr / T
Glycine	Gly / G	Tryptophan	Trp / W
Histidine	His / H	Tyrosine	Tyr / Y
Isoleucine	Ile / I	Valine	Val / V

Classification of amino acids

Since in proteins a-NH₂ and a-COOH groups are involved in amide (peptide) bonds, the classification of amino acids is based on the nature of the group R (side chain) which determines the properties of a protein. On the basis of the physico chemical properties of their side chains, amino acid can be grouped in six different groups which well correspond to those amino acids having high probability to interchange one other during evolution. The letters indicating the six different groups (S, H, N, F, C, V; see below) are referred to as the MDM (Mutation Data Matrix) alphabet.

The Mutation Data Matrix is the result of the comparison of closely related amino acid sequences. From this comparison, Dayhoff (1979) observed that only some amino acid replacements are evolutionary acceptable. For example, tryptophan is more frequently replaced by another aromatic amino acid (phenylalanine and tyrosine) rather than by any another amino acid (see sequences comparison).

 

(S) - Small hydrophylics

  This group comprises glycine, alanine, proline and the two hydroxyacids threonine and serine. They are slightly hydrophylics but do not have ionizable groups at neutral pH, thus they do not contribute to the net charge of proteins.
 

Amino Acid (abbreviations)	pKaCOOH	pKaNH3+
Glycine (Gly or G)	2.34	9.60
Alanine (Ala or A)	2.34	9.69
Threonine (Thr or T)	2.63	10.43	Also classified as an hydroxyamino acid, it has two asymmetric carbon atoms.
Serine (Ser or S)	2.21	9.15	Also classified as an hydroxyamino acid.
Proline (Pro or P)	1.99	10.60

(V) - Small hydrophobics

This group comprises amino acids with aliphatic side chain: valine, leucine, isoleucine and the sulphur-containing methionine. These amino acids do not contribute to the net charge of proteins (at neutral pH).
 

Amino Acid (abbreviations)	pKaCOOH	pKaNH3+	Side chains
Valine (Val or V)	2.32	9.62
Leucine (Leu or L)	2.36	9.60
Isoleucine (Ile or I)	2.36	9.68
Methionine (Met or M)	2.28	9.21

 

(F) - Aromatics

This group includes amino acids having aromatic rings in the side chain: phenhylalanine, tyrosine and tryptophan. Side chains in this group do not have ionizable groups at neutral pH, thus they do not contribute to the net charge of proteins.
 

Amino Acid (abbreviations)	pKaCOOH	pKaNH3+	Side chains
Phenylalanine (Phe or F)	1.83	9.13
Tyrosine (Tyr or Y)	2.20	9.11	pKa phenol group = 10.07
Tryptophan (Trp or W)	2.38	9.39

(N) - Acids and their amides

This group includes amino acids having an additional carboxyl groups in the side chain (aspartic acid and glutamic acid) and their amides (asparagine and glutamine). 

Acids are negatively charged at neutral pH thus contributing to the net charge of proteins.

(H) - Basics

This group includes amino acids having additional amino groups in the side chain (lysine, arginine and histidine). 

They are positively charged at neutral pH thus contributing to the net charge of proteins.

(C) - Sulphydryl

This group includes only cysteine, having an SH group (sulphydril group) in the side chain. 

Cysteine can occur as cystine in which two molecules of cysteines are linked by a disulfide bond. 

SH group is not charged at neutral pH thus this amino acid do not contribute to the net charge of proteins.