A key feature of the present approach is the use of steered MD simulations. Since the WPD loop of PTP1B changes conformation on multi-µs timescales , the simulation length required to observe a number of transitions that is statistically significant is unpractical for routine applications. sMD allows access to such intermediate conformations with simulations on nanoseconds timescales. Sampling of relevant conformations, both of the ligand and the protein, is key to modelling activity probabilities consistent with experimental data. Steering only the active site residues does not ensure the allosteric network will adjust to new conformational states as the WPD loop moves , which causes inconsistent simulation results in disagreement with reported literature values (Supplementary Figure ). Future work may focus on extending the enhanced sampling methodologies used to seed the MSMs to decrease the amount of experimental data required to ensure that the relevant protein conformational states have been sampled.