Linear
and nonlinear dielectric responses of solutions of intrinsically
disordered proteins (IDPs) were analyzed by combining molecular dynamics
simulations with formal theories. A large increment of the linear
dielectric function over that of the solvent is found and related
to large dipole moments of IDPs. The nonlinear dielectric effect (NDE)
of the IDP far exceeds that of the bulk electrolyte, offering a route
to interrogate protein conformational and rotational statistics and
dynamics. Conformational flexibility of the IDP makes the dipole moment
statistics consistent with the gamma/log-normal distributions and
contributes to the NDE through the dipole moment’s non-Gaussian
parameter. The intrinsic non-Gaussian parameter of the dipole moment
combines with the protein osmotic compressibility in the nonlinear
dielectric susceptibility when dipolar correlations are screened by
the electrolyte. The NDE is dominated by dipolar correlations when
electrolyte screening is reduced.