Highlights

  • HADDOCK refinement leads to 98% cryo-EM PPI clash removal
  • Cryo-EM interface contact quality is significantly enhanced by HADDOCK refinement
  • Structural quality of complexes is best preserved in all-atom refinement protocols

Summary

A wide range of cellular processes requires the formation of multimeric protein complexes. The rise of cryo-electron microscopy (cryo-EM) has enabled the structural characterization of these protein assemblies. The density maps produced can, however, still suffer from limited resolution, impeding the process of resolving structures at atomic resolution.

In order to solve this issue, monomers can be fitted into low- to medium-resolution maps. Unfortunately, the models produced frequently contain atomic clashes at the protein-protein interfaces (PPIs), as intermolecular interactions are typically not considered during monomer fitting.

Here, we present a refinement approach based on HADDOCK2.4 to remove intermolecular clashes and optimize PPIs. A dataset of 14 cryo-EM complexes was used to test eight protocols.

The best-performing protocol, consisting of a semi-flexible simulated annealing refinement with centroid restraints on the monomers, was able to decrease intermolecular atomic clashes by 98% without significantly deteriorating the quality of the cryo-EM density fit.

[maxbutton id=”4″ url=”https://doi.org/10.1016/j.str.2022.02.001″ text=”Read More” window=”new” linktitle=”Structure: Interface refinement of low- to medium-resolution Cryo-EM complexes using HADDOCK2.4″ ]

Citation

Tim Neijenhuis, Siri C. van Keulen, Alexandre M.J. J.Bonvin (2022):
Interface refinement of low- to medium-resolution Cryo-EM complexes using HADDOCK2.4.
Structure 30(4)
https://doi.org/10.1016/j.str.2022.02.001