Structural modeling of protein complexes: Current capabilities and challenges

Proteins. 2019 Dec;87(12):1222-1232. doi: 10.1002/prot.25774. Epub 2019 Jul 22.


Proteins frequently interact with each other, and the knowledge of structures of the corresponding protein complexes is necessary to understand how they function. Computational methods are increasingly used to provide structural models of protein complexes. Not surprisingly, community-wide Critical Assessment of protein Structure Prediction (CASP) experiments have recently started monitoring the progress in this research area. We participated in CASP13 with the aim to evaluate our current capabilities in modeling of protein complexes and to gain a better understanding of factors that exert the largest impact on these capabilities. To model protein complexes in CASP13, we applied template-based modeling, free docking and hybrid techniques that enabled us to generate models of the topmost quality for 27 of 42 multimers. If templates for protein complexes could be identified, we modeled the structures with reasonable accuracy by straightforward homology modeling. If only partial templates were available, it was nevertheless possible to predict the interaction interfaces correctly or to generate acceptable models for protein complexes by combining template-based modeling with docking. If no templates were available, we used rigid-body docking with limited success. However, in some free docking models, despite the incorrect subunit orientation and missed interface contacts, the approximate location of protein binding sites was identified correctly. Apparently, our overall performance in docking was limited by the quality of monomer models and by the imperfection of scoring methods. The impact of human intervention on our results in modeling of protein complexes was significant indicating the need for improvements of automatic methods.

Keywords: CAPRI; CASP; binding sites; docking; homology modeling; model quality assessment; protein complexes; protein-protein interactions; scoring; template-based modeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Computational Biology*
  • Databases, Protein
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / ultrastructure*
  • Protein Binding / genetics
  • Protein Conformation*
  • Protein Interaction Mapping
  • Protein Multimerization / genetics
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / ultrastructure*
  • Sequence Analysis, Protein
  • Structural Homology, Protein


  • Multiprotein Complexes
  • Proteins