HENRY M. SOBELL

APPENDIX B - Letter for second discussion

Leonard Lerman writes, “I thought solitons were moving nonlinear excitations -- never stationary. I was surprised to learn that ‘discrete breathers’ can be stationary, and that you envision your ‘premelton’ in DNA to be one such example”.

Henry Sobell replies, “Yes, it is remarkable that ‘discrete breathers’ can arise within a lattice structure and remain stationary during their lifetimes. In addition, discrete breathers demonstrate internal dynamical motion known as “breather motions”. These motions exemplify nonlinear dynamics. We have proposed breather motions to exist within premeltons. Such motions can facilitate the intercalation of a planar drug molecule into DNA, and we will discuss these motions in detail in a subsequent communication”.

(Professor Lerman advanced his intercalation model in 1961 to explain the binding of the aminoacridines to DNA. His model has since been verified by X-ray crystallography is now of wider significance in understanding the dynamic nature of DNA structure).

Peter Leth Christianson writes, “I have just gotten back from a meeting on discrete breathers, and am looking forward to learning more about the structure and properties of premeltons in DNA”.

Henry Sobell replies, “Premeltons are unique in that they contain not one, but two sources of nonlinearity in their structure. This reflects the presence of the beta-DNA structure, a hyperflexible and metastable DNA conformation that emerges (forms) within the premelton. We will discuss how these properties give rise its breather motions. I look forward to hearing your comments regarding this”.

So -- what is the beta-DNA form, and why does this form play such a central role in determining the structure and nonlinear dynamics of the premelton?

To understand this, we must first focus our attention in understanding the conformation of two closely related DNA forms -- B-DNA and A-DNA -- whose diffraction patterns were discovered by Rosalind Franklin in the early 1950’s in her pioneering fiber X-ray diffraction studies. The B-DNA diffraction pattern is observed at high relative humidity, while the A-DNA diffraction pattern is observed at lower relative humidity (75%).

B-DNA is a double helical structure having 10 base pairs per turn in 34.0 Angstroms. Base pairs lie perpendicular to the helix axis, being related by a twist of 36 degrees and a translation along the helix axis of 3.4 Angstroms. Deoxyribose residues are puckered C2’ endo (see the definition of C2’ endo and C3’ endo) and exist in their high anti conformation (this describes the base-sugar orientation around the glycosidic bond that is determined by the torsional angle, chi). The structure has two different 2-fold symmetry axes that relate sugar-phosphate chains. One lies at the level of each base pair (dyad 1), and the other (dyad 2), midway between adjacent base pairs, each being perpendicular to the helix axis.

A-DNA is similar to B-DNA except that it has 11 base pairs per turn in 28.0 Angstroms. Base pairs are tilted 16 degrees to a plane perpendicular to the helix axis, being related by a twist of 32.7 degrees and a translation along the helix axis of 2.54 Angstroms. Deoxyribose residues are C3’ endo, and are oriented relative to the purine or pyrimidine in the low anti conformation. Again, two different symmetry axes are present, one at the level of each base pair, the other midway between two adjacent base pairs. Each is perpendicular to the helix axis.

The B- to A- transition is an example of a structural phase transition, being readily reversed by altering thermodynamic conditions.

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 (or "pinned") by a suitable intercalator or DNA binding protein to be studied in detail.

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.

Evidence for the existence of both the low and high energy beta-DNA forms comes from several sources. These are summarized below:

  1. X-ray crystallographic evidence that indicates the existence of the high energy beta-structural element “pinned” by a class of intercalators called “simple intercalators”.
  2. Fiber X-ray crystallographic evidence that indicates “neighbor-exclusion” by the “simple” platinum organometallointercalator, 2-hydroxyethanethiolato (2, 2', 2’’-terpyridine) platinum (II) when complexed to DNA (these data suggest the presence of the high energy beta-DNA form).
  3. An electron microscopic study of the recA protein: DNA complex that indicates DNA to be stretched one and one-half times, and unwound on the average, 15 degrees every base pair (or 30 degrees every other base pair), relative to B-DNA in its uncomplexed form (these data suggest the presence of the high energy beta-DNA form).
  4. The interactions between a class of molecules known as steroidal diamines and DNA that suggest partial intercalation as their binding mode to DNA (these data suggest the presence of the low energy beta-DNA form).

Henry Sobell
sobell@localnet.com

Alwyn Scott
rover@theriver.com