Which amino acid is most likely to be found in the hydrophobic core of a protein

Amino acids are the compounds or building blocks that make up peptides and proteins. Each amino acid is structured from an amino group and a carboxyl group bound to a tetrahedral carbon. This carbon is designated as the α-carbon (alpha-carbon).

Amino acids differ from each other with respect to their side chains, which are referred to as R groups. The R group for each of the amino acids will differ in structure, electrical charge, and polarity.

Refer to the charts and structures below to explore amino acid properties, types, applications, and availability.

Eleven IMGT 'Physicochemical' classes of the 20 common amino acids have been defined by the physicochemical properties of their side chains (Figure 1) [1].

These standardized classes are used in IMGT® databases and tools, for the description of amino acid class changes in mutations and protein engineering.

Figure 1: The 11 IMGT 'Physicochemical' classes of the 20 common amino acids [1].

The 11 IMGT 'Physicochemical' classes were defined on the 'Hydrophathy', 'Volume', 'Chemical', 'Charge', 'Hydrogen donor or acceptor atoms' and 'Polarity' properties of the side chains (or R- groups).

• 1 class contains 4 amino acids:
• 1 class contains 3 amino acids:
• 4 classes contain 2 amino acids:
  • Sulfur: C, M.
  • Hydroxyl: S, T.
  • Acidic: D, E.
  • Amide: N, Q.
• 5 classes contain a single amino acid: G, F, P, W, Y. They have been individualized from 'Chemical' (G and P from 'aliphatic', F, W and Y from 'aromatic') classes, based on the structural properties of the amino acids in protein domains.

'Hydropathy'

There are 3 IMGT 'Hydropathy' classes. Amino acids in each class are in the order of Table 2 :

• Hydrophobic: A, C, I, L, M, F, W, V.
• Neutral: G, H, P, S, T, Y.
• Hydrophilic: R, N, D, Q, E, K.

Amino acids are ordered from the most hydrophobic one, Isoleucine (I, on the left hand side) to the most hydrophilic one, Arginine (R, on the right hand side), according to the Kyte-Doolitle scale [2].

(1) Tryptophan, despite its value of -0.9 in the Kyte-Doolittle scale, has been classified in the IMGT 'hydrophobic' class, as it participates to the hydrophobic core of the structural domains.

'Volume'

There are 5 IMGT 'Volume' classes (volume in Å3). Amino acids in each class are in the order of Table 2:

• Very small [60-90]: A, G, S.
• Small [108-117]: N, D, C, P, T.
• Medium [138-154]: Q, E, H, V.
• Large [162-174]: R, I, L, K, M.
• Very large [189-228]: F, W, Y.

Amino acids are ordered from the smallest one (G) to the largest one (W).

'Chemical'

There are 7 'Chemical' classes [1]. Amino acids in each class are in the order of Table 2:

• Aliphatic: A, G, I, L, P, V.
• Aromatic: F, W, Y.
• Sulfur: C, M.
• Hydroxyl: S, T.
• Basic: R, H, K.
• Acidic: D, E.
• Amide: N, Q.

'Charge'

There are 3 IMGT 'Charge' classes. Amino acids in each class are in the order of Table 2:

• Positive charged: R, H, K.
• Negative charged: D, E.
• Uncharged: A, N, C, Q, G, I, L, M, F, P, S, T, W, Y, V.

The sulfhydryl group of cystein and phenolic hydroxyl group of tyrosine show some degree of pH-dependent ionization.

'Hydrogen donor or acceptor atoms'

There are 4 IMGT 'Hydrogen donor or acceptor atoms' classes. Amino acids in each class are in the order of Table 2:

• Donor: R, K, W.
• Acceptor: D, E.
• Donor and acceptor: N, Q, H, S, T, Y.
• None: A, C, G, I, L, M, F, P, V.

'Polarity'

There are 2 IMGT 'Polarity' classes, based on the presence or absence of hydrogen donor and/or acceptor atoms. Amino acids in each class are in the order of Table 2:

• Polar: R, N, D, Q, E, H, K, S, T, Y.
• Nonpolar: A, C, G, I, L, M, F, P, W, V.

The 'polar' class comprises amino acids with hydrogen donor and/or acceptor atoms, except tryptophan. Indeed, tryptophan, despite its hydrogen donor atom, has been classified in the IMGT 'nonpolar' class, as it participates to the nonpolar core of the structural domains.Regarding the 'Charge', the 'polar' class includes the 5 charged (R, H, K, D, E) and 5 uncharged (N, Q, S, T, Y) amino acids.

The 'nonpolar' class comprises amino acids without hydrogen donor or acceptor atoms ('none'), and also includes tryptophan. Regarding the 'Charge', the 'nonpolar' class includes the other 10 uncharged (A, C, G, I, L, M, F, P, W, V) amino acids.

Which amino acid would be within the hydrophobic core of this protein?

Which amino acids are considered hydrophobic?

Where in a protein are hydrophobic amino acids most likely to be found?

What type of amino acids would you expect to find at the core in the middle of a water