Our MD analysis shows limited phosphorylation-dependent changes in the equilibria between a range of conformations of the troponin core similar to those known to be on the Ca 2+ activation pathway of troponin consistent with an enhanced probability of the open state on phosphorylation. Phosphorylation results in the rigidification of the overall structure of the troponin complex. We suggest that this stabilises cTnI switch peptide docking to the hydrophobic patch of troponin C in the Ca state and this has an effect on Ca 2+ sensitivity. The observation that an uncoupling mutation induces an opposite change in these metrics on phosphorylation supports this proposition. This could be further tested with other uncoupling mutations or small molecules that can reverse uncoupling ; it is noteworthy that most of the mutations in the troponin core that are reported to uncouple are at the interdomain interface (Supplementary figure ). Rigidification of the overall structure of troponin by mutations, mimicking phosphorylation, may explain how many different mutations in various components of the thin filament, can uncouple .