Forces stabilizing nucleic acid structure: Which interaction provides the greatest stabilizing contribution to double-stranded nucleic acids under physiological conditions?

Introduction / Context:
DNA duplex stability reflects multiple interactions. Distinguishing the dominant contributions helps explain melting behavior, GC-content effects, and sequence-dependent stability in genomics and PCR design.

Given Data / Assumptions:

• Physiological ionic strength where electrostatic repulsion is screened.
• Covalent backbone remains intact; we consider noncovalent interactions.
• Standard B-form DNA considerations.

Concept / Approach:
While hydrogen bonds define base pairing specificity, the major stabilizing force for the helix is base stacking, which is dominated by Van der Waals interactions and hydrophobic effects between adjacent bases. Electrostatics mainly contributes repulsion between phosphates (reduced by cations). Entropy generally disfavors ordered duplex formation.

Step-by-Step Solution:
Acknowledge H-bonds: essential for pairing but not the primary stability driver.Recognize stacking: aromatic bases stack via Van der Waals and hydrophobic interactions.Therefore, Van der Waals (stacking) provides the largest stabilizing contribution.

Verification / Alternative check:
Sequence-dependent melting temperatures correlate strongly with stacking energies (nearest-neighbor parameters), not just number of hydrogen bonds.

Why Other Options Are Wrong:

• Hydrogen bonds: necessary for specificity but contribute less to net stability than stacking.
• Electrostatic bond: phosphate–phosphate interactions are repulsive; cations screen them.
• Conformational entropy: ordering reduces entropy, opposing stability.

Common Pitfalls:
Equating more hydrogen bonds (GC vs AT) with sole stability; the real driver is stacking, though GC stacking is typically stronger.

Final Answer:
Van der Waals