From Protein Structure to Function with Bioinformatics.pdf

3 Comparative Protein Structure Modelling 77Fig. 3.3 Residue energy, using a pairwise statistical potential, is plotted as a function of sequentialresidue positions for two alternative models of the same protein. Negative (blue colour) andpositive (red colour) energies indicate energetically favourable and unfavourable residue environments,respectively. The energy profiles correspond to the models shown on the right with theinaccurate model placed above the more accurate model. Corresponding parts in the models andenergy profiles use the same colour coding scheme while a colourless trace represents the actualexperimental structure3.3 Performance of Comparative Modelling3.3.1 Accuracy of MethodsAn informative way to test protein structure modelling methods, including comparativemodelling, is provided by the biennial meetings on Critical Assessment ofTechniques for Protein Structure Prediction (CASP) (Moult 2005). Protein modellersare challenged to model sequences with unknown 3D structure and to submittheir models to the organizers before the meeting. At the same time, the 3D structuresof the prediction targets are being determined by X-ray crystallography orNMR methods. They only become available after the models are calculated andsubmitted. Thus, a bona fide evaluation of protein structure modelling methods ispossible, although in these exercises it is not trivial to separate the contributionsfrom programs and human expert knowledge.Alternatively a large scale, continuous, and automated prediction benchmarkingexperiment is implemented in the program EVA – EValuation of Automatic proteinstructure prediction (Eyrich et al. 2001). Every week EVA submits pre-releasedPDB sequences to participating modelling servers, collects the results and providesdetailed statistics on secondary structure prediction, fold recognition, comparativemodelling, and prediction on 3D contacts. The LiveBench program has implementedits evaluations in a similar spirit (Bujnicki et al. 2001).