DEPICTER2: a comprehensive webserver for intrinsic disorder and disorder function prediction

Abstract

Intrinsic disorder in proteins is relatively abundant in nature and essential for a broad spectrum of cellular functions. While disorder can be accurately predicted from protein sequences, as it was empirically demonstrated in recent community-organized assessments, it is rather challenging to collect and compile a comprehensive prediction that covers multiple disorder functions. To this end, we introduce the DEPICTER2 (DisorderEd PredictIon CenTER) webserver that offers convenient access to a curated collection of fast and accurate disorder and disorder function predictors. This server includes a state-of-the-art disorder predictor, flDPnn, and five modern methods that cover all currently predictable disorder functions: disordered linkers and protein, peptide, DNA, RNA and lipid binding. DEPICTER2 allows selection of any combination of the six methods, batch predictions of up to 25 proteins per request and provides interactive visualization of the resulting predictions. The webserver is freely available at http://biomine.cs.vcu.edu/servers/DEPICTER2/

Overview Update: Computational Prediction of Intrinsic Disorder in Proteins

“…As these predictive methods and databases mature, research has shifted toward the prediction of various functions of disordered regions (Basu et al., 2023). These functions include protein and peptide binding (Hanson et al., 2020; Katuwawala et al., 2019; Meszaros et al., 2018; Monzon et al., 2021; Peng et al., 2023; Sharma et al., 2019), nucleic acid binding (Barik et al., 2020; Basu et al., 2023; Katuwawala & Kurgan, 2020; Peng & Kurgan, 2015; Zhang et al., 2022), lipid binding (Dobson & Tusnady, 2021; Katuwawala et al., 2021), and disordered linkers (Meng & Kurgan, 2016; Peng et al., 2020). This progress is reflected in the recent CAID experiment, which for the first time included assessment of the predictions of disordered binding regions (Necci et al., 2021).…”

A Functional Map of the Human Intrinsically Disordered Proteome

“…While the presence of IDRs in proteins can generally be predicted with high accuracy from their amino-acid sequences (Emenecker et al 2021;Necci et al 2021), identifying the relationship between the sequences and functions of IDRs remains a difficult task (Basu et al 2023;Chow et al 2023;Hu et al 2021;Lu et al 2022;Pang & Liu 2022;Pritišanac et al 2019;Zarin et al 2019Zarin et al , 2021Zhao et al 2021).…”

“…For intrinsically disordered proteins (IDPs), which are fully disordered and make up ~5% of the human proteome (ca. 1000 proteins) (Tsang et al 2020), predictions of function are even more limited due to the lack of any folded domains (Basu et al 2023).…”

“…While the presence of IDRs in proteins can generally be predicted with high accuracy from their amino-acid sequences (Emenecker et al 2021; Necci et al 2021), identifying the relationship between the sequences and functions of IDRs remains a difficult task (Basu et al 2023; Chow et al 2023; Hu et al 2021; Lu et al 2022; Pang & Liu 2022; Pritišanac et al 2019; Zarin et al 2019, 2021; Zhao et al 2021). Focusing on the segments of IDR sequences that show strong similarity in sequence alignments (which we refer to as “positional conservation”) has provided rich insights into the functions of so-called short-linear motifs (SLiMs) and Molecular Recognition Features (MoRFs) (Davey et al 2023; Kumar et al 2022; Malhis & Gsponer 2015; Mohan et al 2006; Tompa et al 2014).…”