Base-specific contacts — Which amino acid side chains commonly hydrogen-bond directly to DNA/RNA bases?

Introduction:
While basic residues often contact the phosphate backbone, base readout in the grooves relies on side chains capable of forming directional hydrogen bonds. This question focuses on amino acids frequently used for base-specific recognition.

Given Data / Assumptions:

• DNA bases present hydrogen bond donors/acceptors in grooves.
• Protein side chains differ in polarity and H-bonding capacity.
• Specificity requires complementary H-bond patterns.

Concept / Approach:
Asparagine and glutamine possess amide side chains that can both donate and accept hydrogen bonds, making them ideal for precise base recognition. They are common in helix–turn–helix and other DNA binding motifs for reading base identity in the major groove. Other polar residues (e.g., Arg) also contact bases, but among the listed choices, Asn and Gln best represent base-specific hydrogen bonding pairs.

Step-by-Step Solution:

Verification / Alternative check:
Structural databases show frequent Asn/Gln–base contacts in transcription factor–DNA complexes; mutation of these residues often alters sequence specificity.

Why Other Options Are Wrong:

• Cys/Met: limited polar H-bonding; roles include metal binding or hydrophobic packing.
• Lys/Leu: Lys interacts strongly with phosphates; Leu is hydrophobic.
• Ile/Val: hydrophobic; poor H-bond donors/acceptors.
• Gly/Pro: minimal or constrained side chains.

Common Pitfalls:
Assuming any polar residue will give specificity; geometry and dual donor/acceptor capacity are important for accurate base readout.

Final Answer:
Asn and Gln.