Scientific focus


WP1

IDP Function detection

Objectives

WP1 will lay the foundation for detecting IDPs in different contexts. It will provide a complete set of tools for IDR detection from difference sources, including protein sequences, protein structures and literature.
Starting from existing tools already developed by the participants, new detection features will be implemented and integrated in a comprehensive software package (Mobi 2.0) for the analysis of protein structures.

Task list

WP Information

WP type:

research


Duration:

M1 – M29


Person months:

67


WP leader:

UCD, Norman Davey and Denis Shields

  • Task 1.1 – PED pipeline: technical task implying engineering activity
  • Task 1.2 – SLiMs from structure: Detection of short linear motifs from structure is complicated. Simple pattern search generates lot of false positives (FPs) since they are very short (ca. 5 residues). The task will provide new strategies to limit FPs by filtering matches localized to buried residues outside linear structural stretches.
  • Task 1.3 – IDP text-mining: Text-mining is widely used for retrieving functional data from the literature, but a feasibility study focused on intrinsic disorder is missing. The task will test different tools and methods to find the best solution applicable for large-scale automatic searches. This information will then be integrated into existing web server interfaces (WP4) to increase knowledge on experimental IDPs.
  • Task 1.4 – IDR from structure: IDR detection from structural data depends on the type of source. Detection of elongated structures in protein multi-chain X-ray structures will be done by comparing intra- vs. inter-chain residue contacts and training the parameters on the ANCHOR dataset. Moreover, flexible regions will be calculated from B-factor information. Homology transfer is well established for structured domains but very problematic for disordered regions as IDP evolution seems to follow different rules.
  • Task 1.5 – IDR homology transfer: will provide an extensive analysis of the parameters and constraints necessary to safely apply transfer by homology to IDPs based on sequence similarity.
  • Task 1.6 – Mobi 2.0: Technical task implying engineering activity
Deliverables

Software package for the automatic extraction of PED entry data from protein ensembles

Software for automatic detection of IDRs and linear motifs from protein structures

A software tool for the automatic extraction of IDR relevant information from literature

Software for the identification of homologous IDR clusters from sequence databases

New version of the Mobi software