AbstractKinase structures in the inactive “DFG‐out” state provide a wealth of druggable binding site variants. The conformational plasticity of this state can be mainly described by different conformations of binding site‐forming elements such as DFG motif, A‐loop, P‐loop, and αC‐helix. Compared to DFG‐in structures, DFG‐out structures are largely underrepresented in the Protein Data Bank (PDB). Thus, structure‐based drug design efforts for DFG‐out inhibitors may benefit from an efficient approach to generate an ensemble of DFG‐out structures. Accordingly, the presented modeling pipeline systematically generates homology models of kinases in several DFG‐out conformations based on a sophisticated creation of template structures that represent the major states of the flexible structural elements. Eighteen template classes were initially selected from all available kinase structures in the PDB and subsequently employed for modeling the entire kinome in different DFG‐out variants by fusing individual structural elements to multiple chimeric template structures. Molecular dynamics simulations revealed that conformational transitions between the different DFG‐out states generally do not occur within trajectories of a few hundred nanoseconds length. This underlines the benefits of the presented homology modeling pipeline to generate relevant conformations of “DFG‐out” kinase structures for subsequent in silico screening or binding site analysis studies.