10Exterior Loops

10.1 Folding Free Energy Change

Exterior loops are stabilized by terminal mismatches, dangling ends, and coaxial stacks. The stacking is the optimal configuration of dangling ends, terminal mismatches, or coaxial stacks, noting that a nucleotide or helix end can participate in only one of these favorable interactions.

10.2 Folding Enthalpy Change

Similar to free energy change, exterior loop enthalpy changes are the sum of terminal mismatches, dangling ends, and coaxial stacks. The stacking is that of the lowest folding free energy change.

10.3 Example

Free Energy Change

Prediction of Stacking

The predicted stacking configuration is the one with lowest free energy change. There are two possible configurations.

Configuration 1:

Helix 1 with $$5'$$ dangling U, Helix 2 with $$3'$$ dangling C, and Helix 3 with a GG mismatch

ΔG°37 = ΔG°37(AU with $$5'$$ dangling U) + ΔG°37(CG with $$3'$$ dangling C) + ΔG°37(CG with GG mismatch)

ΔG°37 = –0.2 kcal/mol – 0.8 kcal/mol – 1.6 kcal/mol

ΔG°37 = –2.6 kcal/mol

Configuration 2:

Helix 1 in a flush coaxial stack with Helix 2 and Helix 3 with a GG mismatch

ΔG°37 = ΔG°37(coaxial stack of AU followed by GC) + ΔG°37(CG with GG mismatch)

ΔG°37 = –2.08 kcal/mol – 1.6 kcal/mol

ΔG°37 = –3.7 kcal/mol

Therefore, configuration 2, -3.7 kcal/mol, is the predicted free energy change.

Enthalpy Change

Prediction of Stacking

The stacking configuration is fixed by the prediction of folding free energy change and is configuration 2 above.

ΔH° = ΔH°(coaxial stack of AU followed by GC) + ΔH°(CG with GG mismatch)

ΔH° = –10.5 kcal/mol – 9.2 kcal/mol

ΔH° = –19.7 kcal/mol