Predicting Secondary Structure Propensities in IDPs Using Simple Statistics from Three-Residue Fragments

• Published in: Journal of molecular biology 2020-09, Vol.432 (19), p.5447-5459
• Main Authors: Estaña, Alejandro, Barozet, Amélie, Mouhand, Assia, Vaisset, Marc, Zanon, Christophe, Fauret, Pierre, Sibille, Nathalie, Bernadó, Pau, Cortés, Juan
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biochemistry; Biochemistry, Molecular Biology; Bioinformatics; Biophysics; Computer Science; Databases, Protein; Humans; intrinsically disordered proteins; Intrinsically Disordered Proteins - chemistry; Life Sciences; Models, Molecular; molecular recognition elements; Protein Conformation; Protein Structure, Secondary; secondary structure prediction; short linear motifs; Software; structural database
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2020.07.026

Intrinsically disordered proteins (IDPs) play key functional roles facilitated by their inherent plasticity. In most of the cases, IDPs recognize their partners through partially structured elements inserted in fully disordered chains. The identification and characterization of these elements is fundamental to understand the functional mechanisms of IDPs. Although several computational methods have been developed to identify order within disordered chains, most of the current secondary structure predictors are focused on globular proteins and are not necessarily appropriate for IDPs. Here, we present a comprehensible method, called Local Structural Propensity Predictor (LS2P), to predict secondary structure elements from IDP sequences. LS2P performs statistical analyses from a database of three-residue fragments extracted from coil regions of high-resolution protein structures. In addition to identifying scarcely populated helical and extended regions, the method pinpoints short stretches triggering β-turn formation or promoting α-helices. The simplicity of the method enables a direct connection between experimental observations and structural features encoded in IDP sequences. [Display omitted] •Partially structured motifs in IDPs are important for function.•LS2P is a new method to predict secondary structures in IDPs from their sequences.•Simple statistical approach using a structural database of three-residue fragments•LS2P connects sequence with structural features and experimental observations.•LS2P is publicly available through a web server.