title: Dielectric Allostery of Protein: Response of Myosin to ATP Binding.
abstract: Protein uses allostery to execute biological function. The physical mechanism underlying the allostery has long been studied, with the focus on the mechanical response by ligand binding. Here, we highlight the electrostatic response, presenting an idea of "dielectric allostery". We conducted molecular dynamics simulations of myosin, a motor protein with allostery, and analyzed the response to ATP binding which is a crucial step in force-generating function, forcing myosin to unbind from the actin filament. We found that the net negative charge of ATP causes a large-scale, anisotropic dielectric response in myosin, altering the electrostatic potential in the distant actin-binding region and accordingly retracting a positively charged actin-binding loop. A large-scale rearrangement of electrostatic bond network was found to occur upon ATP binding. Since proteins are dielectric and ligands are charged/polar in general, the dielectric allostery might underlie a wide spectrum of functions by proteins.
authors.affiliation: Department of Pure and Applied Physics, Waseda University , Okubo 3-4-1, Shinjuku-Ku, Tokyo 169-8555, Japan.
authors.forename: Takato
authors.identifier: 0000-0002-8510-978X
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Pure and Applied Physics, Waseda University , Okubo 3-4-1, Shinjuku-Ku, Tokyo 169-8555, Japan.
authors.forename: Jun
authors.identifier: 0000-0002-7351-3427
authors.initials: J
authors.lastname: Ohnuki
authors.affiliation: Department of Pure and Applied Physics, Waseda University , Okubo 3-4-1, Shinjuku-Ku, Tokyo 169-8555, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Takano
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000648:ultrastructure; D000255:Adenosine Triphosphate / Q000737:chemistry*; D000494:Allosteric Regulation; D001665:Binding Sites; D056004:Molecular Dynamics Simulation; D009218:Myosins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D055672:Static Electricity
chemical_list: D000255:Adenosine Triphosphate; D009218:Myosins