Hydrodynamic Radii of Intrinsically Disordered Proteins: Fast Prediction by Minimum Dissipation Approximation and Experimental Validation

The diffusion coefficients of globular and fully unfolded
proteins
can be predicted with high accuracy solely from their mass or chain
length. However, this approach fails for intrinsically disordered
proteins (IDPs) containing structural domains. We propose a rapid
predictive methodology for estimating the diffusion coefficients of
IDPs. The methodology uses accelerated conformational sampling based
on self-avoiding random walks and includes hydrodynamic interactions
between coarse-grained protein subunits, modeled using the generalized
Rotne−Prager−Yamakawa approximation. To estimate the
hydrodynamic radius, we rely on the minimum dissipation approximation
recently introduced by Cichocki et al. Using a large set of experimentally
measured hydrodynamic radii of IDPs over a wide range of chain lengths
and domain contributions, we demonstrate that our predictions are
more accurate than the Kirkwood approximation and phenomenological
approaches. Our technique may prove to be valuable in predicting the
hydrodynamic properties of both fully unstructured and multidomain
disordered proteins.