Due to the advancement of proton therapy for cancer treatment, there has been a worldwide increase in the construction of treatment facilities. Therapy centres are often coupled with clinical, biological or material-science research programs. Research activities require proton beams at energies spanning an extensive range with higher beam currents and longer irradiation times than clinical conditions. Additionally, next-generation proton therapy systems are evolving towards more compact designs. In addition to the increased centres’ workloads, reducing the system in size produces a more significant number of secondary particles per unit volume and time. Therefore, the activation level of materials constituting those future proton therapy centres is expected to be higher, increasing the ambient dose and the amount of radioactive waste collected at the end of a centre’s lifetime. These operating conditions pose new challenges for the shielding design and the reduction of the concrete activation. To tackle them, we propose a novel approach to seamlessly simulate all the processes relevant for the evaluation of the concrete shielding activation using, as an illustration, the Ion Beam Applications Proteus® One system. A realistic model of the system is developed using Beam Delivery Simulation (BDSIM), a Geant4-based particle tracking code. It allows a single model to simulate primary and secondary particle tracking in the beamline, its surroundings, and all particle-matter interactions. The code system and library database FISPACT-II allows the computation of the shielding activation by solving the rate equations using ENDF-compliant group library data for nuclear reactions, particle-induced or spontaneous fission yields, and radioactive decay. As input, FISPACT-II is provided with the secondary particle fluences scored using the BDSIM Monte Carlo simulations. This approach is applied to the proton therapy research centre of Charleroi, Belgium. Results compare the evolution of the clearance level and the long-lived ...