Abstract
Understanding the conformational ensemble of an intrinsically disordered protein (IDP) is of great interest due to its relevance to critical intracellular functions and diseases. It is now well established that the polymer scaling behavior can provide a great deal of information about the conformational properties as well as liquid-liquid phase separation of an IDP. It is, therefore, extremely desirable to be able to predict an IDP's scaling behavior from the protein sequence itself. The work in this direction so far has focused on highly charged proteins and how charge patterning can perturb their structural properties. As naturally occurring IDPs are composed of a significant fraction of uncharged amino acids, the rules based on charge content and patterning are only partially helpful in solving the problem. Here, we propose a new order parameter, sequence hydropathy decoration, which can provide a near-quantitative understanding of scaling and structural properties of IDPs devoid of charged residues. We combine this with a charge patterning parameter, sequence charge decoration, to obtain a general equation, parametrized from extensive coarse-grained simulation data, for predicting protein dimensions from the sequence. We finally test this equation against available experimental data and find a semiquantitative match in predicting the scaling behavior. We also provide guidance on how to extend this approach to experimental data, which should be feasible in the near future.