Structurally elucidating transition pathways between protein conformations gives deep mechanistic insight into protein behavior but is typically difficult. Unbiased molecular dynamics (MD) simulations provide one solution, but their computational expense is often prohibitive, motivating the development of enhanced sampling methods that accelerate conformational changes in a given direction, embodied in a collective variable. The accuracy of such methods is unclear for complex protein transitions, because obtaining unbiased MD data for comparison is difficult. Here, we use long-time scale, unbiased MD simulations of epidermal growth factor receptor kinase deactivation as a complex biological test case for two widely used methods-steered molecular dynamics (SMD) and the string method. We found that common collective variable choices, based on the root-mean-square deviation (RMSD) of the entire protein, prevented the methods from producing accurate paths, even in SMD simulations on the time scale of the unbiased transition. Using collective variables based on the RMSD of the region of the protein known to be important for the conformational change, however, enabled both methods to provide a more accurate description of the pathway in a fraction of the simulation time required to observe the unbiased transition.