Nucleic acid design

[2] Heuristic methods use simple criteria which can be quickly evaluated to judge the suitability of different sequences for a given secondary structure.

[2][3] A related heuristic approach is to consider the "mismatch distance", meaning the number of positions in a certain frame where the bases are not complementary.

Another related but more involved approach is to use methods from coding theory to construct nucleic acid sequences with desired properties.

The Gibbs free energy of a perfectly matched nucleic acid duplex can be predicted using a nearest neighbor model.

This model considers only the interactions between a nucleotide and its nearest neighbors on the nucleic acid strand, by summing the free energy of each of the overlapping two-nucleotide subwords of the duplex.

[9] A related approach, inverse secondary structure prediction, uses stochastic local search which improves a nucleic acid sequence by running a structure prediction algorithm and the modifying the sequence to eliminate unwanted features.

This is important because designed nucleic acid complexes usually contain multiple junction points, which introduces geometric constraints to the system.

Because of these constraints, the nucleic acid complexes are sensitive to the relative orientation of the major and minor grooves at junction points.

Models with three pseudo-atoms per base pair, representing the two backbone sugars and the helix axis, have been reported to have a sufficient level of detail to predict experimental results.

[14] Geometrical concerns are especially of interest in the design of DNA origami, because the sequence is predetermined by the choice of scaffold strand.

[2] It can also be used to create sets of nucleic acid strands which are "orthogonal", or non-interacting with each other, so as to minimize or eliminate spurious interactions.

Nucleic acid design can be used to create nucleic acid complexes with complicated secondary structures such as this four-arm junction. These four strands associate into this structure because it maximizes the number of correct base pairs , with A 's matched to T 's and C 's matched to G 's. Image from Mao, 2004. [ 1 ]
Chemical structure of DNA. Nucleic acid double helices will only form between two strands of complementary sequences, where the bases are matched into only A-T or G-C pairs.
A geometrical model of a DNA tetrahedron described in Goodman, 2005. [ 10 ] Models of this type are useful for ensuring that tertiary structure constraints do not cause excessive strain to the molecule.