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Dielectric Allostery of Protein: Response of Myosin to ATP Binding B

Sato, Takato, Ohnuki, Jun, Takano, Mitsunori
The Journal of physical chemistry 2016 v.120 no.51 pp. 13047-13055
adenosine triphosphate, ligands, molecular dynamics, myosin
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.