MFIB: a repository of protein complexes with mutual folding induced by binding

Abstract

Motivation: It is commonplace that intrinsically disordered proteins (IDPs) are involved in crucial interactions in the living cell. However, the study of protein complexes formed exclusively by IDPs is hindered by the lack of data and such analyses remain sporadic. Systematic studies benefited other types of protein-protein interactions paving a way from basic science to therapeutics; yet these efforts require reliable datasets that are currently lacking for synergistically folding complexes of IDPs.

Results: Here we present the Mutual Folding Induced by Binding (MFIB) database, the first systematic collection of complexes formed exclusively by IDPs. MFIB contains an order of magnitude more data than any dataset used in corresponding studies and offers a wide coverage of known IDP complexes in terms of flexibility, oligomeric composition and protein function from all domains of life. The included complexes are grouped using a hierarchical classification and are complemented with structural and functional annotations. MFIB is backed by a firm development team and infrastructure, and together with possible future community collaboration it will provide the cornerstone for structural and functional studies of IDP complexes.

Availability and implementation: MFIB is freely accessible at http://mfib.enzim.ttk.mta.hu/. The MFIB application is hosted by Apache web server and was implemented in PHP. To enrich querying features and to enhance backend performance a MySQL database was also created.

Contact: simon.istvan@ttk.mta.hu, meszaros.balint@ttk.mta.hu.

Supplementary information: Supplementary data are available at Bioinformatics online.

Fig. 1

Workflow of the construction of MFIB. The figure shows the annotation steps of a hypothetical example of three interacting disordered protein regions, where the three chains are annotated through direct, UniRef90-transfer and Pfam-transfer of annotations (marked A, B and C, respectively). Light grey boxes represent disordered protein regions. Smaller black boxes mark regions that are present in the candidate PDB structure. Boxes with dashed outline represent Pfam objects. Arrows show the transfer of annotations either with direct sequence comparisons (direct annotations between UniProt sequences) or with mapping (using Pfam, UniRef90 clusters, or BLAST in the case of transfer between UniRef90 sequences and between UniProt and the PDB candidate proteins)