SCOP2 prototype: a new approach to protein structure mining

Abstract

We present a prototype of a new structural classification of proteins, SCOP2 (http://scop2.mrc-lmb.cam.ac.uk/), that we have developed recently. SCOP2 is a successor to the Structural Classification of Proteins (SCOP, http://scop.mrc-lmb.cam.ac.uk/scop/) database. Similarly to SCOP, the main focus of SCOP2 is to organize structurally characterized proteins according to their structural and evolutionary relationships. SCOP2 was designed to provide a more advanced framework for protein structure annotation and classification. It defines a new approach to the classification of proteins that is essentially different from SCOP, but retains its best features. The SCOP2 classification is described in terms of a directed acyclic graph in which nodes form a complex network of many-to-many relationships and are represented by a region of protein structure and sequence. The new classification project is expected to ensure new advances in the field and open new areas of research.

Figure 1.

SCOP and SCOP2 graphs compared. (Left) A section of the SCOP hierarchical tree, showing the classification into the six obligatory levels: Protein species (SP), Protein (PR), Family (FA), Superfamily (SF), Fold (CF) and Class (CL). The homologous proteins with distinct folds, e.g., the Cro repressors (25), are compulsorily assigned in the same family and so progressively to the same superfamily, fold and class. There is an obligatory node at every level from the root to a leaf, even if such node does not represent any actual relationship, e.g., ‘singleton’ protein family consisting of a single protein that only has a relationship with itself. (Right) In SCOP2, the structural and evolutionary relationships are separated, allowing the classification of the homologous proteins into different folds and structural classes while keeping them in the same evolutionary family and superfamily. Non-obligatory single-child nodes are skipped to emphasize that relatives of a ‘singleton’ protein exist only at the superfamily level. The new category specific to SCOP2, 'other' relationships (IR), is also shown on the graph. These relationships include but are not limited to non-hierarchical relationships between homologous and non-homologous proteins with different folds sharing a large common substructure or motif (see also Figure 2).

Figure 2.

Exploring SCOP2 with a custom graph viewer tool. A screenshot of a SCOP2-graph webpage showing a combined ancestor chart of two orthologous Cro repressors from bacteriophages lambda and p22. (The URL to view this page is http://scop2.mrc-lmb.cam.ac.uk/graph/example1). In addition to the protein relationships, schematically shown in Figure 1, the chart includes additional ‘ontology’ categories. The displayed chart can be expanded or collapsed via the node popup window. The node popup window also displays additional information about the selected node, in particular the associated structural and sequence domains and their boundaries representing the relationship. In this example, the domain, representing the common subfold of the different Cro types, is shown in the context of the full-length protein sequence and structure.