@article {110011,
	title = {Mechanical Coupling in Myosin V: A Simulation Study},
	journal = {Journal of Molecular Biology},
	volume = {395},
	year = {2010},
	pages = {815-833},
	abstract = {Myosin motor function depends on the interaction between different domains that transmit information from one part of the mol. to another.  The interdomain coupling in myosin V is studied with restrained targeted mol. dynamics (MD) using an all-​atom representation in explicit solvent.  To elucidate the origin of the conformational change due to the binding of ATP, targeting forces are applied to small sets of atoms (the forcing sets, FSs) in the direction of their displacement from the rigor conformation, which has a closed actin-​binding cleft, to the post-​rigor conformation, in which the cleft is open.  The "minimal" FS that results in extensive structural changes in the overall myosin conformation is composed of ATP, switch 1, and the nearby HF, HG, and HH helixes.  Addn. of switch 2 to the FS is required to achieve a complete opening of the actin-​binding cleft.  The restrained targeted mol. dynamics simulations reveal the mech. coupling pathways between (i) the nucleotide-​binding pocket (NBP) and the actin-​binding cleft, (ii) the NBP and the converter, and (iii) the actin-​binding cleft and the converter.  Closing of the NBP due to ATP binding is tightly coupled to the opening of the cleft and leads to the rupture of a key hydrogen bond (F441N​/A684O) between switch 2 and the SH1 helix.  The actin-​binding cleft may mediate the rupture of this bond via a connection between the HW helix, the relay helix, and switch 2.  The findings are consistent with exptl. studies and a recent normal mode anal.  The present method is expected to be useful more generally in studies of interdomain coupling in proteins.},
	author = {Victor Ovchinnikov and Bernhardt L. Trout and Martin Karplus}
}
