The following experimental observations are made when a small ligand binds with nanomolar affinity in a deep hydrophobic pocket of the partner protein.
A. The ligand forms a hydrogen bond with a backbone carbonyl oxygen upon binding.
B. Several nonpolar groups in proteins form a hydrophobic network due to the conformational change, leading to the displacement of buried water molecules to the surface.
C. A negatively charged side chain of an amino acid located near the binding site is desolvated.
D. The desolvated side chain of an amino acid located near the binding site does not form a salt bridge with the ligand.
Which one of the following options represents the combination of all correct statement(s) that explain(s) net stabilisation of the ligand:protein complex?

Correct option is A

Correct Answer:
(a) A and B
Explanation:
Formation of a hydrogen bond between the ligand and the protein backbone directly contributes favorably to binding energy (A).
Additionally, hydrophobic interactions and the displacement of ordered water molecules from a deep hydrophobic pocket increase entropy, strongly stabilizing the ligand–protein complex (B).
Thus, statements A and B together best explain the net stabilization.
Information Booster :
· High-affinity ligand binding often combines enthalpic (H-bonds) and entropic (hydrophobic effect) contributions.
· Displacement of buried water molecules is a major driving force in tight binding.
· Backbone interactions are especially valuable because they are less affected by side-chain variability.
· Hydrophobic pockets commonly underlie nanomolar or stronger affinities.
Additional Information (Incorrect Options):
Statement C: Desolvation of a charged residue is energetically unfavorable unless compensated by a strong electrostatic interaction.
Statement D: If a desolvated charged side chain does not form a salt bridge, it leads to destabilization, not stabilization.
Hence, options involving C and/or D alone cannot explain net stabilization.