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The Elastic Properties of the Structurally Characterized Myosin II S2 Subdomain: A Molecular Dynamics and Normal Mode Analysis

Ivana Adamovic ^* , Srboljub M. Mijailovich ^* and Martin Karplus  

^* Harvard School of Public Health, Boston, Massachusetts 02115; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138; and Laboratoire de Chimie Biophysique, Institut de Science et d'Ingénierie Supramoléculaires, Université Louis Pasteur, 67000 Strasbourg, France

Correspondence: Address reprint requests to Srboljub M. Mijailovich, Physiology Program, Dept. of Environmental Health, Bldg. I, Room 1308B, Harvard School of Public Health, 665 Huntington Ave. Boston, MA 02115. Tel.: 617-432-4814; Fax: 617-432-4710; E-mail: smijailo{at}hsph.harvard.edu; or Martin Karplus, Dept. of Chemistry and Chemical Biology, Harvard University, 12 Oxford St., Cambridge, MA 02138. Tel.: 617-495-4018; Fax: 617-496-3204; E-mail: marci{at}tammy.harvard.edu.

The elastic properties (stretching and bending moduli) of myosin are expected to play an important role in its function. Of particular interest is the extended -helical coiled-coil portion of the molecule. Since there is no high resolution structure for the entire coiled-coil, a study is made of the scallop myosin II S2 subdomain for which an x-ray structure is available (Protein Data Bank 1nkn). We estimate the stretching and bending moduli of the S2 subdomain with an atomic level model by use of molecular simulations. Results were obtained from nonequilibrium molecular dynamics simulations in the presence of an external force, from the fluctuations in equilibrium molecular dynamics simulations and from normal modes. In addition, a poly-Ala (78 amino acid residues) -helix model was examined to test the methodology and because of its interest as part of the lever arm. As expected, both the -helix and coiled-coil S2 subdomain are very stiff for stretching along the main axis, with the stretching stiffness constant in the range 60–80 pN/nm (scaled to the 60 nm long S2). Both molecules are much more flexible for bending with a lateral stiffness of 0.010pN/nm for the S2 and 0.0055pN/nm for the -helix (scaled to 60 nm). These results are expected to be useful in estimating cross-bridge elasticity, which is required for understanding the strain-dependent transitions in the actomyosin cycle and for the development of three-dimensional models of muscle contraction.

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