Speaker
Description
We introduce a patchy polymer model as a minimal coarse-grained representation of G4 multimers. G4 multimers are chains of G-quadruplexes, which are stable stacks of guanine-rich tetrads. Because they regulate key genomic processes, G4 multimers are promising targets for designing selective therapeutic ligands. A key open question is how ligand binding modifies the mechanical properties of G4 multimers.
While multiscale and fine-grained computational models can accurately capture these systems, they are often too computationally demanding for broad parameter exploration. To overcome this limitation, we use an extremely coarse-grained model and simulate it with a simple Monte Carlo algorithm. Our approach builds on a Kremer–Grest polymer model calibrated to reproduce the known structural and mechanical properties of G4 multimers from fine-grained references. To investigate selective ligand binding, we extend this framework by introducing discrete attractive patches along the polymer backbone. Ligands can bind specifically to these patches rather than interacting uniformly along the chain, allowing us to model intercalation and stacking in a controlled way. Using this toy model, we systematically study how ligand polymerization and interaction parameters control intercalation, stacking and their effects on polymer mechanics. This provides a simple and versatile platform to explore how ligand architecture and binding specificity can be tuned to modulate the structural and mechanical response of G4-based systems.