Decoding the stabilizing role of spermine on the JX DNA crossover: Insights from all-atom molecular dynamics and quantum-based charge models
Chemical Physics, vol.611, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 611
- Publication Date: 2026
- Doi Number: 10.1016/j.chemphys.2026.113432
- Journal Name: Chemical Physics
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Keywords: Density functional theory (DFT), JX DNA crossover motif, MM/PBSA binding free energy, Molecular dynamics simulation, Spermine (SPM4+), Structural stability
- Istanbul Gelisim University Affiliated: Yes
Abstract
Spermine (SPM4+), a naturally occurring polyamine, plays a key role in modulating DNA conformation through strong multivalent electrostatic interactions. In this study, we investigated the molecular basis of SPM4+ binding and its effect on the structural stability of the jaxtapose crossover (JX) DNA motif, a fundamental component in DNA nanotechnology. The molecular geometry of SPM4+ was first optimized using density functional theory (DFT) with RESP-derived atomic charges, followed by all-atom molecular dynamics (MD) simulations in GROMACS under two ionic regimes: one neutralized by NA+ and the other stabilized by SPM4+. Radial distribution functions, contact statistics, and distance analyses revealed a more intimate and persistent association of SPM4+ with the phosphate backbone than that of NA+, consistent with enhanced multivalent electrostatic coupling. Energetic decomposition and MM/PBSA calculations confirmed markedly more favorable interaction energetics in the SPM4+ environment. Hydrogen-bond analyses demonstrated preservation of canonical base pairing alongside partial dehydration at the DNA interface. Global and local dynamic analyses (RMSD, PCA, and RMSF) indicated reduced conformational fluctuations and enhanced mechanical rigidity under SPM4+ conditions. Overall, SPM4+ effectively neutralizes backbone charge repulsion and reinforces structural cohesion while maintaining canonical B-form geometry. These findings provide mechanistic insight into polyamine-assisted stabilization of DNA crossover motifs and highlight the potential of multivalent polyamines to improve the robustness of crossover-based DNA nanostructures.