TY - JOUR
T1 - Dielectric Allostery of Protein
T2 - Response of Myosin to ATP Binding
AU - Sato, Takato
AU - Ohnuki, Jun
AU - Takano, Mitsunori
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/12/29
Y1 - 2016/12/29
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jpcb.6b10003
DO - 10.1021/acs.jpcb.6b10003
M3 - Article
C2 - 28030954
AN - SCOPUS:85024394762
SN - 1089-5647
VL - 120
SP - 13047
EP - 13055
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 51
ER -