Performance and Its Limits in Rigid Body Protein-Protein Docking

Structure. 2020 Sep 1;28(9):1071-1081.e3. doi: 10.1016/j.str.2020.06.006. Epub 2020 Jul 9.


The development of fast Fourier transform (FFT) algorithms enabled the sampling of billions of complex conformations and thus revolutionized protein-protein docking. FFT-based methods are now widely available and have been used in hundreds of thousands of docking calculations. Although the methods perform "soft" docking, which allows for some overlap of component proteins, the rigid body assumption clearly introduces limitations on accuracy and reliability. In addition, the method can work only with energy expressions represented by sums of correlation functions. In this paper we use a well-established protein-protein docking benchmark set to evaluate the results of these limitations by focusing on the performance of the docking server ClusPro, which implements one of the best rigid body methods. Furthermore, we explore the theoretical limits of accuracy when using established energy terms for scoring, provide comparison with flexible docking algorithms, and review the historical performance of servers in the CAPRI docking experiment.

Keywords: CAPRI; ClusPro docking server; SwarmDock; docking benchmark; docking performance evaluation; fast Fourier transform; flexible docking; scoring function; structure prediction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies / chemistry
  • Antibodies / metabolism
  • Antigens / chemistry
  • Antigens / metabolism
  • Databases, Protein
  • Fourier Analysis
  • Molecular Docking Simulation / methods*
  • Protein Interaction Mapping*
  • Proteins / chemistry
  • Proteins / metabolism


  • Antibodies
  • Antigens
  • Proteins