Charge transport in Deoxyribonucleic acid (DNA) is known to be highly sensitive to the sequence, motivating systematic studies that correlate specific base arrangements with electronic response. We investigate the hole transport characteristics of isomeric DNA hexamers ( \(\text{5}^\prime\) -CGATCG- \(\text{3}^\prime\) and \(\text{5}^\prime\) -CGTACG- \(\text{3}^\prime\) ), to understand the electronic anisotropy introduced by the sequence asymmetry. Classical molecular dynamics (MD) simulations are used to obtain the most probable centroid structure. Density Functional Theory (DFT) calculations are used to construct a real space electronic Hamiltonian, followed by conductance determination within the Landauer-Büttiker formalism. Our results reveal a robust hierarchy where the sequence asymmetry drives orders of magnitude higher conductance of \(\text{5}^\prime\) -CGATCG- \(\text{3}^\prime\) as compared to \(\text{5}^\prime\) -CGTACG- \(\text{3}^\prime\) . The density of states (DOS) distribution over the molecule shows highly delocalized HOMO orbitals are mainly responsible for the higher conductance of \(\text{5}^\prime\) -CGATCG- \(\text{3}^\prime\) . This is also evident from the complementary analysis using Hartree-Fock (HF) calculations. Apart from this, we observe relatively stronger electronic coupling in the central region of \(\text{5}^\prime\) -CGATCG- \(\text{3}^\prime\) as compared to \(\text{5}^\prime\) -CGTACG- \(\text{3}^\prime\) . These findings establish sequence asymmetry as an intrinsic factor governing the charge transport in DNA, with implications for understanding the charge migration in a biological system and the design of DNA-based molecular electronic devices.
