Well-tempered metadynamics was used in order to increase the computational efficiency and recover thermodynamic information on the formation of a surface defect for each surface/solvent combination. In this work, the lag time between bias depositions was set up such that the deposition of biasing potential in the transition state ensemble (λ * ) is limited, following the protocol discussed by Tiwary and Parrinello. The biasing protocol was defined via a trial-and-error procedure with the aim of obtaining an optimal balance between computational efficiency and minimal perturbation. The biasing protocol used to reconstruct the free energy profile of the detachment process is reported in Table .