Half of all deaths from cardiovascular diseases are caused by sudden cardiac death. The kinetic cycle of cardiac myosin is crucial for heart protection and drug development. The state change in the cardiac myosin from the rigor state to the post-rigor state is crucial to explain binding and dissociation with actin filament. Here, we used β-cardiac myosin in the rigor and post-rigor states to model the actomyosin complexes. Molecular dynamics simulations, electrostatic features, and binding energy analysis of actomyosin complexes were performed in the work. Results show that there are weaker interactions and lower electrostatic binding strength in the post-rigor state than the rigor state. In post-rigor state, there were higher free binding energy, fewer salt bridges and fewer hydrogen bonds. Results also showed lower binding affinity in post-rigor state than in rigor state. The decrease in binding affinity provided important conditions for dissociation of the myosin from the actin filament. This research on the mechanism of myosin kinetic cycles provides novel perspectives for future genetic disease studies.

Molecular mechanisms of cardiac actomyosin in the state transformation: A comprehensive study on the binding affinity from rigor to post-rigor state

ACS Spring 2022

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