Evaluating template-based and template-free protein-protein complex structure prediction

UMMS Affiliation

Program in Bioinformatics and Integrative Biology

Publication Date


Document Type



Algorithms; Computational Biology; Databases, Protein; Protein Conformation; *Protein Interaction Domains and Motifs; Protein Interaction Mapping; Sequence Alignment; Software; Structural Homology, Protein


Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Computational Biology | Integrative Biology | Structural Biology | Systems Biology


We compared the performance of template-free (docking) and template-based methods for the prediction of protein-protein complex structures. We found similar performance for a template-based method based on threading (COTH) and another template-based method based on structural alignment (PRISM). The template-based methods showed similar performance to a docking method (ZDOCK) when the latter was allowed one prediction for each complex, but when the same number of predictions was allowed for each method, the docking approach outperformed template-based approaches. We identified strengths and weaknesses in each method. Template-based approaches were better able to handle complexes that involved conformational changes upon binding. Furthermore, the threading-based and docking methods were better than the structural-alignment-based method for enzyme-inhibitor complex prediction. Finally, we show that the near-native (correct) predictions were generally not shared by the various approaches, suggesting that integrating their results could be the superior strategy.

DOI of Published Version



Brief Bioinform. 2014 Mar;15(2):169-76. doi: 10.1093/bib/bbt047. Epub 2013 Jul 1. Link to article on publisher's site

Journal/Book/Conference Title

Briefings in bioinformatics

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Link to Article in PubMed

PubMed ID