Structural Model of Weak Binding Actomyosin in the Prepowerstroke State

We present the first in silico model of the weak binding actomyosin in the initial powerstroke state, representing the actin binding-induced major structural changes in myosin. First, we docked an actin trimer to prepowerstroke myosin then relaxed the complex by a 100-ns long unrestrained molecular dynamics. In the first few nanoseconds, actin binding induced an extra primed myosin state, i.e. the further priming of the myosin lever by 18° coupled to a further closure of switch 2 loop. We demonstrated that actin induces the extra primed state of myosin specifically through the actin N terminus-activation loop interaction. The applied in silico methodology was validated by forming rigor structures that perfectly fitted into an experimentally determined EM map of the rigor actomyosin. Our results unveiled the role of actin in the powerstroke by presenting that actin moves the myosin lever to the extra primed state that leads to the effective lever swing.Actomyosin generates mechanical force in all eukaryotic cells including muscle. Results By dynamic computational simulations we revealed structural rearrangements in myosin upon actin binding, leading to the initial state of force generation. Conclusion The actin binding-induced structural rearrangements in myosin are transmitted specifically through the activation loop of the myosin. Significance The first actomyosin atomic structural model of the initial state of force generation.