Molecular studies of human pentameric ligand-gated ion channels (LGICs) expressed in neurons and at neuromuscular junctions are of utmost importance in the development of therapeutic strategies for neurological disorders. We focus here on the nicotinic acetylcholine receptor nAChR-α7, a homopentameric channel widely expressed in the human brain, with a proven role in a wide spectrum of disorders including schizophrenia and Alzheimer's disease. By exploiting an all-atom structural model of the full (transmembrane and extracellular) protein in the open, agonist-bound conformation we recently developed, we evaluate the free energy and the mean first passage time of single-ion permeation using molecular dynamics simulations and the milestoning method with Voronoi tessellation. The results for the wild-type channel provide the first available mapping of the potential of mean force in the full-length α7 nAChR, reveal its expected cationic nature, and are in good agreement with simulation data for other channels of the LGIC family and with experimental data on nAChRs. We then investigate the role of a specific mutation directly related to ion selectivity in LGICs, the E-1' → A-1' substitution at the cytoplasmatic selectivity filter. We find that the mutation strongly affects sodium and chloride permeation in opposite directions, leading to a complete inversion of selectivity, at variance with the limited experimental results available that classify this mutant as cationic. We thus provide structural determinants for the observed cationic-to-anionic inversion, revealing a key role of the protonation state of residue rings far from the mutation, in the proximity of the hydrophobic channel gate.