Binding Mode Multiplicity and Multiscale Chirality in the Supramolecular Assembly of DNA and a π‐Conjugated Polymer

Abstract

Water-soluble π-conjugated polymers are increasingly considered for DNA biosensing. However, the conformational rearrangement, supramolecular organization and dynamics upon interaction with DNA have been overlooked, which prevents the rational design of such detection tools. To elucidate the binding of a cationic polythiophene (CPT) to DNA with atomistic resolution, we performed molecular simulations of their supramolecular assembly. Comparison of replicated simulations show a multiplicity of CPT binding geometries that contribute to the wrapping of CPT around DNA. The different binding geometries are stabilized by both electrostatic interactions between CPT lateral cations and DNA phosphodiesters and van der Waals interactions between the CPT backbone and the DNA grooves. Simulated circular dichroism (CD) spectra show that the induced CD signal stems from a conserved geometrical feature across the replicated simulations, i. e. the presence of segments of syn configurations between thiophene units along the CPT chain. At the macromolecular scale, we inspected the different shapes related to the CPT binding modes around the DNA through symmetry metrics. Altogether, molecular dynamics (MD) simulations, model Hamiltonian calculations of the CD spectra, and symmetry indices provide insights into the origin of induced chirality from the atomic to the macromolecular scale. Our multidisciplinary approach points out the hierarchical aspect of CPT chiral organization induced by DNA.

A Perspective on Polythiophenes as Conformation Dependent Optical Reporters for Label-Free Bioanalytics

“…It also was shown that rigid−flexible complexes release many more polyions by increasing salt concentration due to limited conformational flexibility. More specific simulations for polythiophene and DNA complexation were presented by Surin and co-workers as shown in Figure 2B and C. 29,69 Figure 2B shows single-stranded (ss) polyA-PT and polyT-PT complexation. Analysis revealed that electrostatic interactions played a pivotal role in PT-DNA complexation.…”

CSM Software: Continuous Symmetry and Chirality Measures for Quantitative Structural Analysis

“…Following this paper, the method was extended to measure chirality and shape . In the following years, the method was applied to study the role of approximate symmetry in numerous molecular systems, including symmetry of crystals, , distortion paths of inorganic complexes, reactive processes, − host–guest interactions, molecular dynamics and symmetry of biomolecules. , Application of this approach beyond chemistry were also documented, e.g., in archeology. , …”