The sensing response of poly(thiophene)s functionalized. with calix[4]arene to Li+, Na+, and K+ has been investigated at the microscopic level using quantum mechanical calculations and molecular dynamics simulations. Results indicate that Na+ interacts electrostatically with the oxygen-rich site of the receptor reducing the conformational flexibility of the polymer backbone. In contrast, Li+ and K+ interact with the tert-butyl groups of the macrocycle enhancing such conformational flexibility. These features arc consistent with available experimental data explaining the selectivity of this material for Na+ over Li+ and K+.