TY - JOUR
T1 - Interface refinement of low- to medium-resolution Cryo-EM complexes using HADDOCK2.4
AU - Neijenhuis, Tim
AU - van Keulen, Siri C.
AU - Bonvin, Alexandre M.J.J.
N1 - Funding Information:
This work was performed with the financial support of the Dutch Foundation for Scientific Research (NWO) (PPS Technology Area grant 741.018.201 ) and the European Union Horizon 2020 project BioExcel ( 823830 ).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/4/7
Y1 - 2022/4/7
N2 - 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.
AB - 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.
KW - atomic clashes
KW - electron density map
KW - HADDOCK
KW - interface quality
KW - protein-protein interfaces
KW - refinement
UR - http://www.scopus.com/inward/record.url?scp=85127339369&partnerID=8YFLogxK
U2 - 10.1016/j.str.2022.02.001
DO - 10.1016/j.str.2022.02.001
M3 - Article
C2 - 35216656
AN - SCOPUS:85127339369
SN - 0969-2126
VL - 30
SP - 476-484.e3
JO - Structure
JF - Structure
IS - 4
ER -