Minimum dissipation approximation: A fast algorithm for the prediction of diffusive properties of intrinsically disordered proteins

Diffusion coefficients of globular and completely disordered proteins can be predicted with a high degree of accuracy based solely on the mass of the protein. However, this approach fails when the disordered protein contains structured domains. To provide quantitative predictions in such cases, we present a rapid predictive methodology for the estimation of the diffusion coefficients of intrinsically disordered proteins irrespectively of the presence of structured domains. The method takes advantage of the expedited conformational sampling based on self-avoiding random walks, and includes hydrodynamic interactions between coarse-grained protein subunits, modelled in the generalised Rotne-Prager-Yamakawa approximation. To estimate the hydrodynamic radius, we rely on the novel minimal dissipation algorithm. We demonstrate on a selection of measured hydrodynamic radii of IDPs that our methodology provides more accurate predictions than classical methods without imposing considerable computational burdens. We anticipate that our approach may prove useful for fully disordered and multidomain proteins.