Certain combinations of nucleotides can lower energy when they occur at the first unpaired positions of a loop. These positions are sometimes called "boost points".


The energy of loops in EteRNA is determined by the last paired base of any attached stacks and the first unpaired bases of the loop.

These are known as the closing base pair and terminal mismatch, respectively. The most common and effective method of boosting involves the creation of terminal GA mismatches.

How do I boost?Edit

See also: List of Boosting Guides
  • Identify what kind of loop are you trying to boost. Internal loops, external loops, multiloops, and most hairpin loops can be boosted, but each type of loop is boosted in a different way. Bulges and 3-nt hairpin loops (triloops) cannot be boosted.
  • Find the loop's boost points and place the required nucleotides. If you do not know where the boost points are or what nucleotides to place, look at the summary below or consult one of the boost guides.
  • Consider alternative boosting. Many loops can be boosted in more than one way. Certain difficult puzzles require unconventional boosts.

Internal LoopsEdit

Most internal loops can be boosted by the formation of GA, AG, and UU terminal mismatches. All other mismatches have no impact on loop energy.

Two approaches to boosting are shown In the image to the right. The leftmost structure is unboosted. The middle structure is boosted with two UU mismatches. The rightmost structure is boosted with two GA mismatches. {C}The 1-1, 2-2, 1-2, and 2-1 internal loops each have special energy terms.

Hairpin LoopsEdit

Most hairpin loops can be boosted in way similar to internal loops, by the formation of GA and UU terminal mismatches. Triloops cannot be boosted, and tetraloops have special energy terms.

In hairpin loops, however, the G of the GA mismatch must be at the lowest-numbered position of the loop (the 5'-most position). If the G is placed at the highest-numbered position, the energy bonus is much lower or nonexistent.

Certain terminal mismatches - typically CA, CC, and CU - are more destabilizing than the default AA mismatch. This can be exploited to destabilize unwanted hairpins that form in a puzzle.

Multiloops and External LoopsEdit


Multiloops and external loops are boosted in the same manner. The images to the right illustrate all possible energy-lowering combinations for simple multiloops.

Location of Boost PointsEdit

Each stack attached to a multiloop/external loop may create a boost point. The location of this boost point and the type of nucleotide required is determined by the type and orientation of the closing base pair.

Terminal MismatchEdit

An AG or CA terminal mismatch is always used to boost a multiloop or external loop. The two mismatches are not interchangeable, however. A loop that can be boosted by an AG mismatch cannot be boosted by a CA mismatch.

Other terminal mismatches can increase free energy beyond that of an unboosted, all-A multiloop. This can be exploited to to stabilize multiloops attached to internal loops.

Loops with Closely-Spaced StacksEdit

Energy is calculated differently for multiloops and external loops with stacks separated by 0 or 1 unpaired nucleotides. The location of boost points and nucleotide(s) required depend on the arrangement of stacks and choice of closing pairs.

Due to the large number of possible combinations, the higher starting energy of these loops, boosting these structures is not always a simple or straightforward task.

Special LoopsEdit

For energies of 1-1, 2-1, 1-2, and 2-2 loops, see: Drake's Advanced Puzzle Solving Guide.
For energies of tetraloops, see: Dimension9's List of Tetraloop Sequences.

Certain small internal loops and hairpins are particularly well-studied, and a more detailed set of parameters is used to model their energy. The number of possible sequences is very large, even for these small loops. The resources above contain a fairly exhaustive list of sequences. The most commonly-used are described below.

1-1 LoopsEdit

The energy of a 1-1 loop with a GG mismatch is always negative, regardless of closing pair. When flanked by two GC closing pairs, the GA, UU, CU, and CA mismatch can also have energy equal to or below zero.

2-1 and 1-2 LoopsEdit

The loop sequences GA/G, AG/G, GG/A, GC/A, UC/U, and UU/U have lower energy than the all-A loop. The GC/A and GG/A mismatch are useful when solving adjacent 2-1 loops.

2-2 LoopsEdit

The 2-2 loop can range in energy from below -4 to over +2. In most cases, opposing GU mismatches of the type 5'-XUGY-3' (where X and Y make any base pair) have an energy of -2.5 kcal or lower.


The lowest-energy tetraloop sequences in EteRNA are members of the GNRA and UNCG tetraloop families. The GAAA tetraloop is often the simplest and lowest-energy option, however. The GAGA tetraloop closed by a GU pair has an energy of 2.3 kcal, and can be useful when solving certain puzzles.

Unboostable LoopsEdit

Bulges, 3-nt haripin loops, and multiloops with no unpaired bases are impossible to boost.

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