The activation loop (A-loop) is a flexible structural region responsible for the kinase's catalytic function. It can adopt either an extended, active conformation and a folded, inactive conformation (Figure ). The N-terminal end of the A-loop is close to the ATP binding site, and the phosphorylation of the A-loop serves as a critical regulatory mechanism for kinase activation. Also at the N-terminal end of the A-loop lies a conserved Asp-Phe-Gly motif, commonly termed the DFG motif. This motif can adopt several conformations, including DFG-in, DFG-out, or an intermediate state occasionally observed called DFG-inter depending on the relative location of the aspartate and the phenylalanine residue (Figure ). Active kinases typically adopt the DFG-in conformation, and an inactive state adopts the DFG-out conformation, where the aspartate residue rotates away from the ATP-binding site, impairing catalytic function while simultaneously exposing an allosteric pocket. Drugs binding to DDR1 can target either the DFG-in state, competing with ATP (Type-I inhibitors), or the DFG-out state at the allosteric pocket (Type-II inhibitors), locking the kinase in its inactive state. The conformational state of the DFG motif is typically defined using two structural metrics known as the Dunbrack distances, which measure the distance from the terminal atom of the DFG-phenylalanine to two anchor atoms within the nearby αC helix. Conformations are classified as DFG-in, DFG-out, or DFG-inter based on these distances, while structures that fall outside these defined thresholds are labeled as "unassigned". Similarly, the A-loop conformation can be commonly assessed by the distance between residues R191 and D110, which form a potential salt bridge. For this study, we characterized the A-loop conformation using the distance between their C β atoms. The af2rave protocol identifies 8 states of the system with distinct A-loop conformations and DFG labels (Figure ). Figure af2rave reaches similar level of sampling as millisecond long MD Another aim of the af2rave protocol is to facilitate sampling by selecting well-chosen starting structures. Instead of relying on long MD simulations to cross free energy barriers spontaneously, starting from diverse configurations in multiple basins can be equivalent to "tunneling" through those barriers, with the goal of achieving comparable coverage of conformational space through shorter MD simulations. In this approach, AlphaFold2 serves as a hypothesis generator, while the feature selection module clusters the generated structures into diverse MD-starting configurations.