We report the results of a new global QCD analysis, which includes deep-inelastic e /μ scattering data off proton and deuterium, as well as Drell-Yan lepton pair production in proton-proton and proton-deuterium collisions and W±/Z boson production data from p p and p p ¯ collisions at the LHC and Tevatron. Nuclear effects in the deuteron are treated in terms of a nuclear convolution approach with bound off-shell nucleons within a weak binding approximation. The off-shell correction is controlled by a universal function of the Bjorken variable x , describing the modification of parton distributions in bound nucleons, which is determined in our analysis along with the parton distribution functions of the proton. A number of systematic studies are performed to estimate the uncertainties arising from the use of various deuterium datasets, from the modeling of higher twist contributions to the structure functions, from the treatment of target mass corrections, as well as from the nuclear corrections in the deuteron. We obtain predictions for the ratios F2n/F2p, and d /u , focusing on the region of large x . We also compare our results with the ones obtained by other QCD analyses, as well as with the recent data from the MARATHON experiment.