DNA origami nanotweezer as a programmable nanoligand holder: A hybrid ANM-oxDNA simulation study

DNA origami nanodevices enable programmable control of nanoscale motion and force transduction through sequence-defined structural design. Understanding how ligand attachment geometry affects their mechanical response requires quantitative modeling frameworks that couple molecular recognition to structural mechanics. Here, we employ a hybrid anisotropic network model (ANM)-oxDNA simulation approach to characterize the thermomechanical behavior of a ligand-functionalized DNA origami nanotweezer. The enzyme KDPG aldolase is used as a model ligand, covalently linked via single-stranded DNA handles to predefined attachment domains along the nanotweezer arms. Systematic equilibrium and near-quasi-static simulations reveal how attachment distance, temperature, and ligand multiplicity govern the stiffness, rupture dynamics, and free-energy landscapes of the complex. The hybrid ANM-oxDNA framework enables direct mapping of ligand-induced mechanical coupling and provides transferable insight into the design of hybrid DNA-protein assemblies. This study establishes a general computational methodology for linking biochemical interaction geometry to mechanical energetics in DNA origami systems, facilitating the rational design and optimization of reconfigurable nanoscale mechanisms.