Q.28 Amino acid residue which is most likely to be found in the interior of water-soluble globular
proteins is
(A) Threonine (B) Aspartic acid (C) Valine (D) Histidine

Amino Acid in Protein Interior: Valine Dominates Globular Cores

Water-soluble globular proteins fold with hydrophobic residues like valine buried inside to avoid water, while hydrophilic ones stay on the surface. Valine stands out as the top choice among the options for interior positioning due to its nonpolar nature.​

Correct Answer

The amino acid residue most likely found in the interior of water-soluble globular proteins is Valine (C). Hydrophobic amino acids cluster in the protein core to stabilize the structure through van der Waals interactions, shielding them from the aqueous environment.​

Why Valine Fits the Interior

Valine features a branched, nonpolar isopropyl side chain (-CH(CH₃)₂) that repels water, making it ideal for the hydrophobic core of globular proteins. This positioning minimizes free energy by promoting tight packing in the interior. Studies confirm valine’s prevalence in buried sites compared to polar residues.​

Threonine Analysis

Threonine (A) has a polar, uncharged side chain with a hydroxyl group (-CH(OH)CH₃), rendering it hydrophilic and prone to hydrogen bonding with water. Such properties position it more often on protein surfaces or active sites rather than interiors.​

Aspartic Acid Breakdown

Aspartic acid (B) carries a negatively charged carboxylic acid side chain (-CH₂COOH) at physiological pH, making it highly hydrophilic and ionic. Charged residues like this favor solvent-exposed surfaces to interact with water and maintain solubility.​

Histidine Evaluation

Histidine (D) possesses an imidazole ring in its side chain, which is polar and can be charged (pKa ~6.0), enabling roles in catalysis or metal binding. Though sometimes internal, its amphoteric nature makes it less hydrophobic than valine, so it often appears on surfaces.​