Both thermodynamic selectivity and kinetic selectivity are important determinants for the in vivo efficacy of candidate drug molecules. Computational tools to predict thermodynamic and kinetic parameters are therefore necessary for the screening stage of the drug-design pipeline. As the timescale of most drug (un)binding processes is out of reach for conventional molecular dynamics simulations, specialized methodologies are needed to determine the (un)binding rates and residence times of protein-drug complexes. To assess the kinetics, most methods require the definition of a reaction coordinate that accurately describes the progression of the (un)binding process. As these (un)binding pathways are not known a priori, it is possible that free energy barriers are hidden along degrees of freedom (DoFs) that are orthogonal to the low-dimensional and user-defined reaction coordinate, resulting in inaccurate kinetics. In this study, Replica Exchange Transition Interface Sampling (RETIS) [1] is used to investigate the orthogonal DoFs in the unbinding pathways of imatinib to the kinase protein ABL (wild type and mutated variants). RETIS is an exact path sampling method, which generates trajectories using shooting moves, and which accepts or rejects trajectories using a Monte Carlo algorithm. RETIS is reaction-coordinate independent and produces reactive trajectories as if they originated from a long molecular dynamics simulation. As such, the hidden energy barriers should be captured by the paths generated by RETIS, which will be presented here. Reference [1] R. Cabriolu, K. M. Skjelbred Refsnes, P. G. Bolhuis, and T. S. Van Erp, “Foundations and latest advances in replica exchange transition interface sampling,” J. Chem. Phys., vol. 147, no. 15, 2017.