  Protein-ligand (un)binding simulations are a recent focus of biased molecular
dynamics simulations. Such binding and unbinding can occur via different
pathways in and out of a binding site. We here present a theoretical framework
how to compute kinetics along separate paths and to combine the path-specific
rates into global binding and unbinding rates for comparison with experiment.
Using dissipation-corrected targeted molecular dynamics in combination with
temperature-boosted Langevin equation simulations [Nat. Commun. \textbf{11},
2918 (2020)] applied to a two-dimensional model and the trypsin-benzamidine
complex as test systems, we assess the robustness of the procedure and discuss
aspects of its practical applicability to predict multisecond kinetics of
complex biomolecular systems.
