lowest energy statehighest energy state

(Top illustration). A-DNA, beta-DNA and B-DNA, and their associated sugar-pucker conformations. The lowest energy beta-DNA form is a metastable structure, with helical parameters intermediate between A- and B- forms. For comparative purposes, each figure contains 20 base pairs.

(Bottom illustration). Beta-DNA is a hyperflexible structure that exists in many different energy states. It is bounded on the left by its lowest energy state, and on the right by its highest energy state. Steroidal diamines such as irehdiamine A, stabilize the lowest energy state by partial intercalation, while planar drugs and dyes such as ethidium, stabilize the highest energy state by complete intercalation. The lowest energy state is an obligatory structural intermediate in the B- to A- transition, whereas the highest energy state is a transition state intermediate in DNA melting.

Beta-DNA is a distinctly different structural phase from either A- or B- DNA. It is both metastable and hyperflexible and, for this reason, must be held ("pinned") by a suitable intercalator or DNA binding protein to be studied in detail. The underlying source of nonlinearity that separates beta-DNA from either A- or B-DNA is the presence of both C2' endo and C3' endo sugar pucker conformations.

The structure is composed of repeating units called beta-structural elements. These are a family of base-paired dinucleotide structures, each possessing the same mixed sugar-pucker pattern (i.e., C3' endo (3'-5') C2' endo) and having similar backbone conformational angles, but varying in the degree of base unstacking. Lower energy beta-structural elements contain base pairs partially unstacked, while higher energy beta-structural elements contain base pairs completely unstacked.

Why is beta-DNA a metastable structural phase?

This reflects the presence of additional energies in its lowest energy structure that necessitate base pairs within beta-structural elements to remain partially unstacked. For example, partial base pair unstacking may be required to relieve strain energy in the sugar-phosphate backbone (and/or elsewhere in the structure) as the lowest energy beta-DNA structure emerges from A- or B-DNA.

Why is beta-DNA a hyperflexible structural phase?

The presence of partial base pair unstacking acts to weaken van der Waals forces stabilizing stacking interactions between base pairs. In addition, the altered sugar-phosphate backbone stereochemistry present within each beta-structural element allows DNA to stretch and to unwind due to the presence of unhindered rotation around glycosidic bonds and other sugar-phosphate linkages. These combined effects give the beta-structural element hinge-like properties, and explain why beta-DNA is a hyperflexible structural phase.