TIM-Finder: a new method for identifying TIM-barrel proteins

Abstract

Background: The triosephosphate isomerase (TIM)-barrel fold occurs frequently in the proteomes of different organisms, and the known TIM-barrel proteins have been found to play diverse functional roles. To accelerate the exploration of the sequence-structure protein landscape in the TIM-barrel fold, a computational tool that allows sensitive detection of TIM-barrel proteins is required.

Results: To develop a new TIM-barrel protein identification method in this work, we consider three descriptors: a sequence-alignment-based descriptor using PSI-BLAST e-values and bit scores, a descriptor based on secondary structure element alignment (SSEA), and a descriptor based on the occurrence of PROSITE functional motifs. With the assistance of Support Vector Machine (SVM), the three descriptors were combined to obtain a new method with improved performance, which we call TIM-Finder. When tested on the whole proteome of Bacillus subtilis, TIM-Finder is able to detect 194 TIM-barrel proteins at a 99% confidence level, outperforming the PSI-BLAST search as well as one existing fold recognition method.

Conclusions: TIM-Finder can serve as a competitive tool for proteome-wide TIM-barrel protein identification. The TIM-Finder web server is freely accessible at http://202.112.170.199/TIM-Finder/.

Figure 1

The TIM-barrel fold. (a) Cartoon representation of the 3D structure of a typical TIM-barrel protein (triosephosphate isomerase, PDB entry: 8tim). (b) The SCOP statistics on the TIM-barrel fold.

Figure 2

The overall performance of three descriptors individually measured by ROC analysis.

Figure 3

The CE structural alignment of two TIM-barrel proteins 1vpqA and 1i60A. Although the PSI-BLAST-based descriptor was not able to detect the remote homologous relationship between 1vpqA (green) and 1i60A (yellow), the SSEA-based descriptor can successfully recognize their structural similarity based on a SSEA score of 0.814.

Figure 4

Cartoon representation of a TIM-barrel protein (PDB entry: 1n55). The structural location of the most frequently occurred PROSITE motif (entry: PS00171, pattern: [AVG]- [YLV]-E-P- [LIVMEPKST]- [WYEAS]- [SAL]- [IV]- [GN]- [TEKDVS]- [GKNAD]) in the 3D model is shown in magenta.

Figure 5

The overall performance of TIM-Finder measured by ROC analysis.