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A helix folds only when stacking beats loop entropy

Supplied working report; original verdicts not validated.

Review status: Held for correction. This is an archival source note, not a passed proof.

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# A helix folds only when stacking beats loop entropy

**XXII, Theory 10 / Molecular / RNA structure** · verdict: **supported**

Claim (verbatim):
> RNA secondary structure is set by the ratio of base-pairing energy to loop entropy, so a helix forms only when the pairing gain exceeds the cost of closing a loop.

## Result

The minimum stem required to fold rises from 3 bp for a 4-nt loop to 5 bp for a 1000-nt loop: the pairing gain must grow to cover the loop-entropy cost.

## Headline

Minimum stem to fold grows from 3 to 5 bp as the loop lengthens from 4 to 1000 nt.

## Design

Hairpin free energy was modelled as stem stacking gain minus a loop-initiation plus length-dependent entropy cost; the smallest stem giving a stable fold was found for loop sizes spanning 4-1000 nt.

## Key statistics

- min_stem_loop4 = 3 bp
- min_stem_loop30 = 4 bp
- min_stem_loop300 = 5 bp
- min_stem_loop1000 = 5 bp

## Predictions

- **P1** (supported): minimum stem rises 3 -> 5 bp as loop grows

## Limitations

- Mean stacking and loop-entropy parameters are simplifications of the full nearest-neighbour model.
- The model ignores coaxial stacking, ion effects and tertiary contacts.
- The log dependence of loop entropy means the threshold stem grows only slowly with loop size.

Provenance: Jacobson-Stockmayer loop entropy with a loop-initiation penalty and mean NN stacking.

*Working paper — not peer reviewed. AI-assisted. Not medical, clinical, financial or safety advice.*

Included code and results