not-yet-known not-yet-known not-yet-known unknown The electronic properties of DNA make it an attractive candidate for applications in biosensing and molecular electronics. One approach to utilizing DNA in these fields involves binding molecules, such as aptamers, to control DNA’s electrical conductance and serve as biosensors. To further explore the potential of DNA-aptamer complexes for such applications, we model and simulate the binding of G-quadruplex aptamers to double-stranded DNA (dsDNA) and examine its impact on the structural and electrical properties of dsDNA. By combining molecular dynamics simulations and density functional theory with Green’s function-based charge transport calculations, we gain insights into how the aptamer modifies the spacing between base pairs near the binding site, enhancing electronic coupling and creating a conductive path near the highest occupied molecular orbital (HOMO). This interaction results in a significant modulation of conductance by at least 47 times higher than that of dsDNA without the aptamer. We anticipate that our findings will promote the development of DNA-aptamer complexes for use in molecular electronics and biosensing applications.