A new computational framework based on multiscale modeling approach is developed to calculate the current–voltage (V–I) characteristics of a double stranded DNA (dsDNA) attached between two gold electrodes in different fashion. We also provide framework to calculate the electronic coupling between the DNA base and gold electrode using first principle calculations. For the hole transport, coupling for the connections of 3’ end of dsDNA to the electrode was found to be ∼0.06 eV which was almost ∼3 times stronger than the coupling for the 5’ connection (∼0.02 eV). These coupling parameters are used for both the incoherent hopping transport (Marcus-Hush type) calculation and the coherent tunneling calculation (Landauer-B"uttiker approach) to predict the charge transport behavior for dsDNA of different lengths. We discovered that the conductance of the dsDNA strongly depends on how the dsDNA ends are attached to the electrode. The anisotropic transport is visible in both incoherent hopping and coherent tunneling calculation suggesting robustness of the phenomena. Our calculation suggests that connecting different dsDNA ends with the electrode, one can achieve different resistance of the dsDNA, which widens the applicability of the dsDNA in various molecular electronic devices.