Book of Abstracts: Albany 2007
June 19-23 2007
DNA-Threading Intercalation Rate Studies: Dynamics is an Efficient Mechanism for Biomolecular Structure Recognition
The talk will first illustrate the use of polarized-light spectroscopy: "site-specific linear dichroism by molecular replacement" (SSLD) for structural characterisation of ?difficult? biomolecular systems not amenable to NMR or X-ray crystal study, such as fibrous protein-DNA or fluidic peptide-membrane structures (1, 2). Insight from LD has inspired us to design and study new DNA ligands: for dinuclear ruthenium polypyridine complexes time-resolved binding geometry measurements reveal rearrangements, which are extremely slow, from groove-binding geometry into threading intercalation geometries (3, 4).
We speculate about the existence of two, potentially also biologically relevant, dynamic interaction mechanisms that we denote: ?Hydrophobic Catalysis? (HC) and ?Kinetic Recognition? (KR). With the latter, KR, we mean a binding selectivity effect caused by site-specific molecular dynamics, far from equilibrium, as e.g. demonstrated by long alternate AT stretches which due to faster base-pair opening dynamics become transient targets for threading intercalators. The longer-range attractive electrostatics and associated entropic contributions to the attractive free energy can be thought of as less structurally discriminative than the short-range repulsive interactions that characterize high-energy landscapes and barriers associated with low entropies. As a conseqence, the mutually orthogonal thermodynamic and dynamic scenes could play quite different roles in biological recognition and we suggest that kinetic recognition can be the more effective one under certain conditions. We further note that hydrophobicity of auxiliary moieties of the threading compounds, as well as presence of aggregates of co-ionic amphiphile molecules, such as SDS micelles (5), can significantly reduce the activation energies of binding and dissociation kinetics (Hydrophobic Catalysis).
References and Footnotes
Physical Chemistry, Department of Chemical and Biological Engineering,
Chalmers University of Technology, SE-412 96 Gothenburg, Sweden