title: Early stages of the recovery stroke in myosin II studied by molecular dynamics simulations.
abstract: The recovery stroke is a key step in the functional cycle of muscle motor protein myosin, during which pre-recovery conformation of the protein is changed into the active post-recovery conformation, ready to exersice force. We study the microscopic details of this transition using molecular dynamics simulations of atomistic models in implicit and explicit solvent. In more than 2 μs of aggregate simulation time, we uncover evidence that the recovery stroke is a two-step process consisting of two stages separated by a time delay. In our simulations, we directly observe the first stage at which switch II loop closes in the presence of adenosine triphosphate at the nucleotide binding site. The resulting configuration of the nucleotide binding site is identical to that detected experimentally. Distribution of inter-residue distances measured in the force generating region of myosin is in good agreement with the experimental data. The second stage of the recovery stroke structural transition, rotation of the converter domain, was not observed in our simulations. Apparently it occurs on a longer time scale. We suggest that the two parts of the recovery stroke need to be studied using separate computational models.
authors.affiliation: Department of Physics and Optical Science, University of North Carolina Charlotte, Charlotte, North Carolina 28262, USA. abaumket@uncc.edu
authors.forename: Andrij
authors.initials: A
authors.lastname: Baumketner
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nesmelov
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D056004:Molecular Dynamics Simulation; D024462:Myosin Type II / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D012997:Solvents
chemical_list: D012997:Solvents; D000255:Adenosine Triphosphate; D024462:Myosin Type II