What is BISC?

BISC (BInary SubComplexes in proteins) is a new protein-protein interaction (PPI) database intending to bridge between the two communities most active in their characterisation: structural biology and functional genomics researchers. BISC allows users to explore known and modellable subcomplex structures in current functional genomics PPI databases in user-friendly manner. It is organized in three main sections:

  1. Characterised SubComplexes (BISCHom + BISCHet)
    This section contains binary substructures extracted from crystallographically determined structures in the PDB and predicted biological assemblies based on their coordinates by PISA. Homodimeric and heterodimeric interfaces are separated for further analysis, since the latter are evolutionarily more constrained with respect to mutations, due to their symmetry. Homedimeric interfaces have sequence identity at least 95% over 95% of the sequence length.
  2. Modellable Interactions in Functional Genomics Databases (BISC-MI)
    BISC-MI features a list of modellable interactions in three of the most widely used databases of experimentally reported PPI: the BioGRID, IntAct and HPRD. These PPI share sequence similarity between both partners and a template structure in BISCHom or BISCHet.
  3. Data and tool-linkouts for validating analysis using structural bioinformatics
    Users may want to inspect the surface properties of the template and/or modelled subcomplexes, e.g. electrostatic charge and hydrophobicity. Validation programs can help evaluate the feasibility of a hypothetical PPI e.g. by evaluating complementarity at the two interacting protein surfaces. However, some require special input files (e.g. the web/Java tool MolSurfer and the validation program SCOTCH), or are difficult for non-experts to interpret (e.g. PISA prediction output). Information from these programs is easily obtained from BISC pages.

Please send an email to juettemann (a t) soe.ucsc.edu.

How do I search BISC?

Characterised SubComplexes (BISCHom + BISCHet)

Users can search by keyword or sequence similarity (with either of two suspected interaction partners, or both) (snapshot) to retrieve an informative BISC page for each subcomplex of interest (snapshot). Alongside fully interactive, embedded Jmol displays emphasising the interface, structural information and links are provided, e.g. SCOP classification of both partners; interface size and residues (buried surface area computed by NACCESS) and energy scores by PISA. Importantly the subcomplexes can serve as potential template structures for modelling protein complexes by homology

Modellable Interactions in Functional Genomics Databases (BISC-MI)

Users can generate protein structural models dynamically, by an automated procedure using the program MODELLER. Multiple sequence alignments (MSAs) for each partner family are generated beforehand because MSA-based modelling generally delivers better models than pair-wise alignment procedures. The output page (snapshot) is returned by email-reply and provides embedded interactive displays of the two protein family MSAs (using Jalview) and the model (and a link for downloading the atomic coordinates).

Please note that BISC produces theoretical, unproven models, which must be considered with care. Unless the target and template sequences are identical the model provides an unproven 3D-rendition of a potential subcomplex between the two partner proteins, based on homology to a structurally characterised subcomplex. No more, no less. Please validate any functional speculation based on this model through further experimental or computational analyses.

While it is importance to stress the speculative and unproven nature of any such model, it can often serve as a valuable starting point for further validation.

How do I ask questions?

Please email juettemann (a t) soe.ucsc.edu