Abstract
BackgroundAlthough methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. Previously we have discussed the basic mechanisms of our novel method for structure comparison based on our TOPS+ model (Topological descriptions of Protein Structures Enhanced with Ligand Information). In this paper we show how these results can be significantly improved using parameter optimization, and we call the resulting optimised TOPS+ method as advanced TOPS+ comparison method i.e. advTOPS+.ResultsWe have developed a TOPS+ string model as an improvement to the TOPS [1-3] graph model by considering loops as secondary structure elements (SSEs) in addition to helices and strands, representing ligands as first class objects, and describing interactions between SSEs, and SSEs and ligands, by incoming and outgoing arcs, annotating SSEs with the interaction direction and type. Benchmarking results of an all-against-all pairwise comparison using a large dataset of 2,620 non-redundant structures from the PDB40 dataset [4] demonstrate the biological significance, in terms of SCOP classification at the superfamily level, of our TOPS+ comparison method.ConclusionsOur advanced TOPS+ comparison shows better performance on the PDB40 dataset [4] compared to our basic TOPS+ method, giving 90% accuracy for SCOP alpha+beta; a 6% increase in accuracy compared to the TOPS and basic TOPS+ methods. It also outperforms the TOPS, basic TOPS+ and SSAP comparison methods on the Chew-Kedem dataset [5], achieving 98% accuracy.Software AvailabilityThe TOPS+ comparison server is available at http://balabio.dcs.gla.ac.uk/mallika/WebTOPS/.
Highlights
Methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance
Analysis of results for the PDB40 dataset Figure 1 shows the Receiver Operating Characteristics (ROC) curves and Table 1 gives AUC values for SCOP classes all-alpha, all-beta, alpha/beta and alpha+beta on the PDB40 subset dataset obtained from the TOPS, TOPS+ and advanced TOPS+ methods
The results show that the advTOPS+ method is superior to TOPS+ on classes all-beta, alpha/ beta and alpha+beta with 82%, 77% and 90% accuracy; while it gives similar results on the allalpha class with an accuracy of 82%
Summary
Methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. As a result the number of known structures in the Protein Data Bank (PDB) [7] is increasing rapidly every year and currently holds 59,790 structures (August 25, 2009) This highlights the importance of the need for fast and reliable protein structure comparison methods. GRATH [15] is a graph-based algorithm that compares the axial vectors of alpha helices and beta strands of two proteins, together with the distances, angles and chirality between these vectors It is based on a method by Grindley et al [16]. TOPS is a graph-based method applied to the topological representation of the protein structures [3] These methods perform very fast protein structure comparison in most cases the results have significantly less biological interpretation due to the abstract nature of the protein model. The current version of the SCOP database classified the (single) TIM barrels protein fold into 33 distinct functional superfamilies
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