SWII in closed and open structural states was observed experimentally with X-ray crystallography, when myosin is trapped with a nucleotide analog.27–29 These data were in agreement with nucleotide chase experiments,4,30–32 which show slower rate of ATP dissociation than ADP, indicating closed conformation of SWII when ATP is bound and open SWII conformation with bound ADP. According to atomic structures, closed and open structural state of SWII is accompanied with bent and straight relay helix accordingly, and initially it was proposed that closed SWII and bent relay helix are rigidly coupled in one myosin structural state (M**). These structural rearrangements were interpreted as a reason for myosin intrinsic fluorescence change, observed earlier in kinetic studies of skeletal myosin.33 Indeed, the surface accessibility area of one of myosin tryptophans (W501) changes substantially during the M* M** structural transformation. But myosin W501 single tryptophan mutant shows unexpected drop of intrinsic fluorescence at initial stage of myosin–ATP interaction, indicating that other tryptophans (there are five tryptophans total in the skeletal myosin head) play a role in the intrinsic fluorescence change. Skeletal myosin has two tryptophans close to the nucleotide binding site, and the attempt to detect nucleotide binding kinetics and possibly kinetics of structural rearrangement of SWII was made with single tryptophan myosin mutants, when tryptophan was engineered near nucleotide binding site (W113, W129, and W131).34 Unfortunately, these tryptophans were insensitive to SWII closure upon myosin–ATP interaction. Studies of spin labeled nucleotide analogs, bound to myosin, showed immobilization of the spin label upon nucleotide binding, but it was concluded that spin labeled nucleotide was not sensitive to SWII structural state.35 Studies of fluorescent (mant) nucleotide binding to myosin concluded that fluorescence change of mant nucleotide upon its binding to myosin reflects only binding event and not SWII closure.32 Temperature jump studies2, 6 showed that intrinsic fluorescence of myosin, trapped with a nucleotide analog, changes upon temperature jump, reflecting myosin conformation change with the same nucleotide analog bound. These were the first experimental results indicating that structures of the SWII and the relay helix are not rigidly coupled in M* and M** structural states of myosin. Recently, continuous wave EPR, pulsed EPR, and FRET studies of myosin, labeled with spin or fluorescent probes and trapped with nucleotide analogs, confirmed loose coupling between biochemical state of myosin (determined by bound nucleotide and as a result, closed or opened SWII) and the structural state of the force generating region.7 Our simulations confirm these recent experimental results, showing the absence of strict correspondence between the SWII and the relay helix structural states, and proposing that the SWII closure and structural changes in the force generating region are occurring at different times during the recovery stroke.