The Structure Superposition Database

Abstract

The need for new tools for investigating biological systems on a large scale is becoming acute, particularly with respect to computationally intensive analyses such as comparisons of many three-dimensional protein structures. Structure superposition is a valuable approach for understanding evolutionary relationships and for the prediction of function. But while available tools are adequate for generating and viewing superpositions of single pairs of protein structures, these tools are generally too cumbersome and time-consuming for examining multiple superpositions. To address this need, we have created the Structure Superposition Database (SSD) for accessing, viewing and understanding large sets of structure superposition data. The initial implementation of the SSD contains the results of pairwise, all-by-all superpositions of a representative set of 115 (beta/alpha)8 barrel structures (TIM barrels). Future plans call for extending the database to include representative structure superpositions for many additional folds. The SSD can be browsed with a user interface module developed as an extension to Chimera, an extensible molecular modeling program. Features of the user interface module facilitate viewing multiple superpositions together. The SSD interface module can be downloaded from http://ssd.rbvi.ucsf.edu.

Figure 1

Schematic representation of SSD data structures. The enolase superfamily (blue) contains multiple homologous proteins. All of these proteins (MR, enolase, …), along with a protein from a different superfamily (PRAI) (peach) can be compared. Each protein has an associated structure (magenta). One set of MinRMS results (green) compares two structures and includes multiple superpositions (cyan) with different numbers of alpha-carbons matched (n).

Figure 2

Screenshot of SSD search options in the left frame of the SSD user interface module. The search options are: (A) view structures sorted by superfamily, (B) search for a single structure, (C) search for superpositions of a pair of structures, (D) search for superpositions of all structures within a user-defined group and (E) specify visualization options.

Figure 3

Viewing multiple superpositions together. The menu options (A) for viewing a group of proteins allow the user to view superpositions for a pair of proteins (B) or more than two proteins superimposed together (C). When multiple structures are superimposed relative to one template, the scores for each pairwise superposition are displayed in a table that provides the RMSD values representing the comparison of the template structure to each structure checked in the list (D). The structures are displayed in the main Chimera window. The structure-based sequence alignment is shown through the Multalign Viewer interface (E), which connects the sequence alignments to the graphical display of structures.