Polyelectrolytes (PEs) are common semi-conductive polymers with hydrophilic ionic or ionizable side groups and hydrophobic π-conjugated backbone. The conjugated PEs have adjustable structural properties, so they have been widely synthesized and used in diverse areas such as targeted molecule detections, detecting genetic disorders, biomedical applications, solar cells, light-emitting diodes, and photovoltaics studies [[1], [2], [3]]. Moreover, they have an important place in the literature owing to their water solubility and sensitive optical responses to external factors (temperature, light, pH, solvent, binding to other molecules, etc.) [3,4].

Polythiophene (PT) and its derivatives are the most used water-soluble conjugated PEs. Their optical and electronic properties form a unique substructure for bio- and chemo-sensor developments. Because of their low toxicity and good photostability in living-cell experiments, they have been broadly studied for sensing biological targets such as polysaccharides, proteins, folic acid, adenosine triphosphate (ATP), deoxyribonucleic acid (DNA) [[5], [6], [7], [8], [9], [10]]. In particular, cationic PTs (CPT) have a significant role in biosensor development to be selective and sensitive probes due to their intermolecular interaction with DNA. In 2005, Leclerc et al. [6] have been reported conformational transitions caused by the complexation of single-stranded DNA (ssDNA) with a CPT derivative. The optical signals were followed without labeling the target or probe to provide the specific detection of nucleic acids. The PTs with various cationic side groups have been synthesized and mixed with ssDNA at an equal molar ratio by Rubio-Magnieto and co-workers [2] to determine the effects of PTs’ backbone structures and the behavior of charged groups when binding to DNA. Carreon et al. [4] have studied the suitability of CPTs, which contain tertiary and quaternary amine, to bind DNA by electrostatic interactions. Some studies about the electrostatic interactions between biological molecules like ssDNA or double-stranded DNA (dsDNA) and CPT derivative have been summarized by Zheng and He in 2014 [11]. The study shows that the fluorescence of the polymer is quenched when CPTs are mixed with ssDNA, and a color change has been observed from yellow to red. The formation of complexes has been tracked by UV–visible absorption spectroscopy, fluorescent spectroscopy, nuclear magnetic resonance (NMR), and circular dichroic (CD) spectroscopy. These results were accounted for by the structural changes from a random coil to a flat conformation upon complex formation [11]. Ammanath et al. [12] have recently developed a simple colorimetric and fluorescence probe by using PT derivative for profiling advanced glycation end products (AGEs).

The changes in the polymer structure and the interactions between PT derivatives and DNA can be examined using computational methods. Molecular dynamics (MD) simulation is the most preferred computational method for large systems. One of the studies in the literature done by Preat et al. [13] in 2011 includes MD simulations of several duplexes formed by ssDNA and PT derivatives at the atomistic level. The possible interactions which triggered complex formation, such as electrostatic interactions (positive charges in PT derivatives and negative charges in DNA phosphates) and other specific interactions (O–H, S–H, π-π stacking, etc.), have been used in the analyses of their simulations. Another study in 2015 involved a combined experimental and computational work by Rubio Magnieto et al. [10]. Self-assembly between DNA and PT derivative has been linked to a balance between π-type and electrostatic intermolecular interactions. It has been indicated that MD simulation results support the experimental spectra (CD and UV–vis spectra). In our previous work [14], Chemistry at Harvard Macromolecular Mechanics (CHARMM) [15] compatible force field for a CPT derivative (see Fig. 1, a)) which has the potential of sensing biological molecules have been generated, and MD simulations for 20-mer and its complexes formed with AMP and ATP have been carried out. The response of the 20-mer to the addition of ATP causes a strong red shift in UV-VIS spectra. In that work, we have suggested that this might be explained by weak π-cation interactions in the ATP complex. These interactions may prevent the complex structure from a random coil form.

In the present work, CHARMM compatible force field has been generated for another CPT shown in Fig. 1b. MD simulations have been performed to investigate the nature of conformational changes in the CPT when ssDNA is added. The dominant type of interactions in the complexes will be explored via the MD simulation analyses to understand the behavior of complexes.