Presence of Nonlinear Excitations in DNA Structure and Their Relationship to DNA Premelting and to Drug Intercalation

Abstract

We propose that collectively localized nonlinear excitations (solitons) exist in DNA structure. These arise as a consequence of an intrinsic nonlinear ribose inversion instability that results in a modulated βalternation in sugar puckering along the polymer backbone. In their bound state, soliton-antisoliton pairs contain β premelted core regions capable of undergoing breathing motions that facilitate drug intercalation. We call such bound state structures -- β premeltons. The stability of a β premelton is expected to reflect the collective properties of extended DNA regions and to be sensitive to temperature, pH, ionic strength and other thermodynamic factors. Its tendency to localize at specific nucleotide base sequences may serve to initiate site-specific DNA pre-melting and melting. We suggest that β premeltons provide nucleation centers important for RNA polymerase-promoter recognition. Such nucleation centers could also correspond to nuclease hypersensitive sites.

The possibility that nonlinear excitations (solitons) exist in biopolymers and play a central role in energy transfer was first advanced by Davydov in his classic series of papers (1–3). In addition, a different class of solitons that give rise to localized conformational changes in DNA structure has been proposed by Englander et al. to explain DNA breathing phenomena (4).

Solitons are intrinsic locally coherent excitations that move along a polymer chain with a velocity significantly less than the speed of sound (they may even be stationary). They are combinations of intramolecular and deformational excitations that appear as a consequence of an intrinsic nonlinear instability in the polymer structure.

Extensive research on solitons in many physical systems has shown that this nonlinearity gives the spacially localized conformational excitation a robust character (5,6). Solítons do not significantly interact with conventional normal mode excitations (i.e., phonons). They have their own identity and can be treated by Newtonian dynamics as heavy Brownian-like particles, each having an “effective mass”. Solitary structures -- as sites for biochemical activity -- behave like independent species and can be treated by statistical mechanics and chemical thermodynamics. They can arise from equilibrium or nonequilibrium processes.

Here, we propose that localized nonlinear excitations -- solitons -- exist in DNA. These arise as a consequence of an intrinsic nonlinear instability in DNA structure which is primarily associated with inter-conversions between the two predominent sugar-pucker conformations, C2’ endo and C3’ endo. In their bound state, soliton-antisoliton pairs surround β premelted core regions -- these regions can undergo breathing motions that facilitate the intercalation of drugs and dyes into DNA. Similar bound state structures could act as phase boundaries that connect different DNA forms.

Several communications describing our ideas have already appeared (7–9). Here, we develop these ideas in greater detail.