Sequence- and Size-Dependent Interactions between Cysteine-Functionalized CdTe Nanoparticles and DNA

Understanding how functionalized nanoparticles interact with double-stranded DNA at the interface is essential for two purposes. It helps interpret nanoparticle-induced nucleic acid deformation and guides the design of DNA-active nanomaterials. Here, we use all-atom molecular dynamics simulations, umbrella sampling, and electrostatic/contact analyses to examine the sequence and DNA-size dependence of the interactions between a cysteine-functionalized CdTe nanoparticle and dsDNA, with groove geometry serving as a key interfacial binding mode. For both 32-bp DNA sequences studied, nanoparticle binding is attractive in both groove orientations, but the major-groove pathway is consistently more favorable than the minor-groove pathway. The free-energy minimum for the GATATC-containing DNA is deeper than that for the ATCGAT mutant, especially in the major groove, indicating clear sequence dependence in groove-mediated interfacial binding. Structural analysis further shows that stronger major-groove binding is associated with more extensive nanoparticle-DNA contacts and a more favorable local electrostatic environment. Nanoparticle adsorption induces measurable DNA bending. The bending response follows the same trend as the interfacial binding strength. Specifically, major-groove binding produces stronger bending than minor-groove binding. The GATATC-containing DNA bends more strongly than the ATCGAT mutant. The bending response also weakens with increasing DNA size, as the duplex length increases from 32 bp to 80-90 bp. Analyses of base stacking and phosphodiester-bond fluctuations further indicate that local structural stability differs between A-T and G-C base pairs. These local differences contribute to the observed DNA bending. These results define the CdTe nanoparticle-DNA interaction as a sequence- and size-dependent interfacial recognition process that is mediated by groove-dependent binding, in which interfacial contacts, electrostatic interactions, sequence, and DNA length jointly govern binding free energy and DNA deformation.