Ligands in the PTP1B series contain a hinge, and as such proved to be a more challenging set to dock, with one ligand failing to redock under all docking protocols due to a steric clash with the receptor. Of the remaining ligands, their orientation in the binding pocket was consistently predicted differently from the modelled poses in all but the Glide MCS protocols. Similarly to P38α, a fallback core constraint of 1 Å was required to allow the remaining ligands to dock with the fixed core constraint, which resulted in a flipped core being observed for several poses in the Glide coreconstrained protocol. Vanilla Glide docking also suffered from a poorly positioned core in some cases (Figure ). Vanilla Vina generated a mix of Similarly to P38α, PTP1B's reference poses were extensively hand-modelled in the original publication. This is reflected in the reduced RMSD and increased τ values for the reference computations compared to all tested docking protocols. Nevertheless, all protocols were able to recover the expected trend in experimental binding affinities, with core-constrained Glide producing the worst correlation (Kendal's τ= 0.1). Interestingly, the MCS-filtered Vina together with vanilla Glide pro-tocols achieved the lowest RMSE (0.8 kcal/mol) and AUE (1.1 kcal/mol) among the docking protocols. Also, the worst performing unguided vanilla Vina protocol (RMSE=1.5, AUE=1.1 kcal/mol) performed comparably with the best performing MCS Glide protocol (RMSE=1.2 kcal/mol, AUE=0.9 kcal/mol).