Intrinsically disordered proteins (IDPs) do not have a static tertiary structure but fluctuate between unfolded and partially folded states. This conformational plasticity is fundamental for their biological activity as regulatory elements in the cell ^[1]. The unfolded nature of IDPs is encoded in their primary structure ^[2] and, therefore, can be predicted from the polypeptide sequence. Multiple computational tools, exploiting diverse physicochemical protein principles, have succeeded in identifying disordered proteins in standard conditions ^[3], yet without considering environmental variables such as pH in their algorithms. In a recent study, we modeled protein disorder as a function of pH and developed a disorder predictor able to anticipate disorder-to-order transitions in IDPs named DispHred ^[4]. Still, DispHred was limited to the prediction of a unique polypeptide sequence at a time, precluding the study in proteomes. With DispHScan we addressed this need providing a new tool that expanded the capabilities of our original method allowing the study of pH-dependent protein disorder for multiple sequences.

2. DispHScan Pipeline