Quality assessment of protein model-structures based on structural and functional similarities

Bogumil M Konopka,Malgorzata Kotulska,Jean-Christophe Nebel

doi:10.1186/1471-2105-13-242

Abstract

BackgroundExperimental determination of protein 3D structures is expensive, time consuming and sometimes impossible. A gap between number of protein structures deposited in the World Wide Protein Data Bank and the number of sequenced proteins constantly broadens. Computational modeling is deemed to be one of the ways to deal with the problem. Although protein 3D structure prediction is a difficult task, many tools are available. These tools can model it from a sequence or partial structural information, e.g. contact maps. Consequently, biologists have the ability to generate automatically a putative 3D structure model of any protein. However, the main issue becomes evaluation of the model quality, which is one of the most important challenges of structural biology.ResultsGOBA - Gene Ontology-Based Assessment is a novel Protein Model Quality Assessment Program. It estimates the compatibility between a model-structure and its expected function. GOBA is based on the assumption that a high quality model is expected to be structurally similar to proteins functionally similar to the prediction target. Whereas DALI is used to measure structure similarity, protein functional similarity is quantified using standardized and hierarchical description of proteins provided by Gene Ontology combined with Wang's algorithm for calculating semantic similarity. Two approaches are proposed to express the quality of protein model-structures. One is a single model quality assessment method, the other is its modification, which provides a relative measure of model quality. Exhaustive evaluation is performed on data sets of model-structures submitted to the CASP8 and CASP9 contests.ConclusionsThe validation shows that the method is able to discriminate between good and bad model-structures. The best of tested GOBA scores achieved 0.74 and 0.8 as a mean Pearson correlation to the observed quality of models in our CASP8 and CASP9-based validation sets. GOBA also obtained the best result for two targets of CASP8, and one of CASP9, compared to the contest participants. Consequently, GOBA offers a novel single model quality assessment program that addresses the practical needs of biologists. In conjunction with other Model Quality Assessment Programs (MQAPs), it would prove useful for the evaluation of single protein models.

Highlights

Experimental determination of protein 3D structures is expensive, time consuming and sometimes impossible
Comparisons were conducted with all Model Quality Assessment Program (MQAP) that took part in the CASP8 and CASP9 events
Dali Z-scores of Structural Neighbors (SNs, see Methods) of each protein were plotted against their corresponding Functional Similarity (FS) scores (Figure 1)

Summary

Introduction

Experimental determination of protein 3D structures is expensive, time consuming and sometimes impossible. In order to address this challenge of structural biology, many methods have been proposed These MQAPs fall within two main categories: consensus and single model approaches. The latest evaluation of MQAPs reports that, consensus methods perform generally well, they are usually unable to extract the best model from a list; their strength seems to be mainly in discriminating between good and bad models [10]. They highlight that the usage of consensus methods is quite limited for biologists since they are generally interested in estimating the quality of a single model

Methods

Results

Conclusion