Proteins linear polymers built of amino acids. The sequence of the amino acids decide the 3 dimensional fold of the protein. The sequence of amino acid also defines the flexibility or rigidity of an protein. This structural property crucial to the protein functions. There are 20 commonly occurring amino acids in nature. A protein can contain any combination and number of the these 20 amino acids.

Proteins contain a wide range of functional groups such as thiols, alcohols, carboxamides and many more. The chemical activity of these functional groups is essential for the function of proteins.

Amino Acids

Amino acids are small molecules that contain:

• an alpha carbon C-α
• an amino group NH₂
• a carboxyl group COOH
• the R side chain

The R group distinguishes one amino acid from another. Furthermore, the side chain is responsible for the specific chemical properties of the amino acid.

19 of the 20 common amino acids have a chiral α-carbon atom. Gly does not. Mirror image pairs of amino acids are designated by L (levo) and D (dextro). Proteins are assembled from L amino acids. Only a few D amino acids occur in nature. Almost all sugars have a D conformation. Threonine and isoleucine have 2 chiral carbons each, thus producing 4 possible stereoisomers each. Isomers depend on the position of the 4 group around the chiral center. Amino acids are L or D depending on the position of the amino group.

Classification of Amino acids

Based on the table above, the amino acids can be classified into several groups.

Charged Amino acids

Charged amino acids are overall uncharged but have even charge distribution.

Acidic / negatively charged amino acids: ED
Basic / positively charged amino acids: KRH

Hydrophobic amino acids - FW MAIL PGV

Polar - SCN WYTH

Polar amino acids are overall uncharged but uneven charge distribution.

Memorizing amino acids

Memorizing the 20 amino acids is among the most undesirable things a life students has to do. All biology, biochemistry and other life sciences students are required to 'know' the amino acids for one of more exams. This knowledge comes in very useful even after you have succeeded in your exam. Following is what you need to know about amino acids:

• amino acid names
• 3 letter abbreviations
• 1 letter abbreviations
• polarity
• acidity / basicity
• hydrophobicity
• structures

The best way to memorize is to associate something you would like to retain with something you already know. In addition, committing things to your memory gradually over time is a better way to memorize than trying to memorize everything all at once. The best approach to memorizing amino acids is to use logic, name recognition and similarities rather than differences. Learning amino acids in detail now would allow you to acquire a better understanding of proteins structure later on.

Memorizing abbreviations

The following tips were devised by my biochemistry 101 buddies and myself. They seem rather awkward but they help us avoid confusion to this day. It is amazing as to how often, people confuse the amino acids.

• The first step is to start with the logical ones. A C G L I M P S T V. Memorize them back and forth between names, 3 letter abbreviations and 1 letter abbreviations.
• Once you got them right, you can move to the ones which have a sound related to the abbreviation. F N R Y. Repeat Phenylalanine, Arparagine, Arginine, Tyrosine stressing the F N R and Y.
• Now on to the confusing ones. Leucine-Lysine (L-K) and Glycine-Glutamine (G-Q). I refer to Lysine as Kysine and to Glutamine and Qutamine.
• D and E are the two acidic ones. A in Asp comes before in G in Glu, so Asp gets a D and Glu gets an E

Memorizing amino acid classifications

• There are only two amino acids which have the word acid attached to them; aspartic acid and glutamic acid. Guess what, they are both acidic. Another way to remember is just to associate the name ED with acidic.
• To memorize, you basically need to find something with KRH, KHR, HKR, HRK, RHK, or RKH. You can google these terms but you won't find anyting better than King's Royal Horse. This would help you remember that K, R, and H belong in the same classification but won't help you in remembering which classification. So adding a B verb for basic would be helpful. For example, buried kings royal horse or bought kings royal horse, etc.
• We you have lots of amino acids in a group, it helps to break them down. Hydrophobic: FW MAIL PGV. Polar: SCN WYTH.

Memorizing amino acid structures

Our strategy is to memorize one structure and use it to infer another. So let's begin with the easier one. Glycine.

           COOH     Glycine
         α |        
  +H3N --- C --- H
           |
           H

When we replace the H with a methyl group, we get Alanine.

           COOH     Alanine
         α |        
  +H3N --- C --- H
           |
           CH3

When we add a phenyl group to alanine, we get phenylalanine.

           COOH     Phenylalanine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
          / \
         | O |
          \ /

When we add a hydroxyl group to Phe, we get Tyrosine.

           COOH     Tyrosine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
          / \
         | O |
          \ /
           |
           OH

There are only 2 acidic amino acids. To be acidic, they must have a negatively charged R side chain. This negative charge is provided by COO^-. Aspartic acid is formed by adding a carboxyl ion to Alanine:

           COOH     Aspartic Acid
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           COO-

Glutamic acid is formed by inserting another CH₂ into Aspartic acid:

           COOH     Glutamic Acid
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           CH2
           |
           COO-

In un-ionized form, glutamic acid and aspartic acids are called glutamate and aspartate. Glutamine and Asparagine are amide derivatives of Glu and Asp.

           COOH     Asparagine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           C=O
           |
           NH2

           COOH     Glutamine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           CH2
           |
           C=O
           |
           NH2

All three basic amino acids (KRH) have a positive charge on the nitrogen in the R side chain.

           COOH     Lysine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           CH2
           |
           CH2
           |
           CH2
           |
           NH3+

           COOH     Arginine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           CH2
           |
           CH2
           |
           NH
          /
    +H2N=C
          \
           NH2

           COOH     Histidine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           Imidazole

Serine is formed by adding a hydroxyl group to Alanine.

           COOH     Serine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           OH

Threonine is formed by adding a CH₃ to Serine.

           COOH     Threonine
         α |        
  +H3N --- C --- H
           |
         H-C-OH
           |
           CH3

Cysteine is formed by replacing the O with S in Serine.

           COOH     Cysteine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           SH

           COOH     Methionine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           CH2
           |
           S
           |
           CH3

Valine has a V shaped side chain

           COOH     Valine
         α |        
  +H3N --- C --- H
           |
           CH
          / \
        CH3   CH3

Leucine has a Y shaped side chain.

           COOH     Leucine
         α |        
  +H3N --- C --- H
           |
           CH2
           |
           CH
          / \
        CH3   CH3

Isoleucine has a upside down L-shaped side chain.

           COOH     Isoleucine
         α |        
  +H3N --- C --- H
           |
         H-C-CH3
           |
           CH2
           |
           CH3

Proline is shaped lika a pentagon with the amino group incorporated in the ring.

          COOH     Proline
        α |        
   HN --- C --- H
    |     |
    CH2   CH2
     \   /
      CH2

Stereochemistry

19 of the 20 common amino acids have a chiral alpha-carbon atom. Gly does not. Mirror image pairs of amino acids are designated by L (levo) and D (dextro). Proteins are assembled from L amino acids. Only a few D amino acids occur in nature. Threonine and isoleucine have 2 chiral carbons each, thus producing 4 possible stereoisomers each.

Isomers depend on the position of the 4 group around the chiral center. Amino acids are L or D depending on the position of the amino group.

           COOH               COOH     
         α |                α |       
  +H3N --- C --- H      H --- C --- NH3+
           |                  |
           CH3                CH3
      L-Alanine            D-Alanine

pH & pKa

pKa values of amino acid side chains play an important role in defining the pH-dependent characteristics of a protein. The pH-dependence of the activity displayed by enzymes and the pH-dependence of protein stability, for example, are properties that are determined by the pKa values of amino acid side chains.

Amino acids have weak acid and weak basic character. Low pH transition leads to titration of the carboxylic group. High pH transition leads to titration of the amino group. pI is a point at which there is no net charge. The Zwitterionic form is the most populated form at neutral pH.

At pKa, fully half of the molecules are protonated and the other half are deprotonated.