Integrative Modeling of Biomolecular Complexes: HADDOCKing with Cryo-Electron Microscopy Data.
Protein-protein interactions play a central role in all cellular processes. Insight into their atomic architecture is therefore of paramount importance. Cryo-electron microscopy (cryo-EM) is capable of directly imaging large macromolecular complexes. Unfortunately, the resolution is usually not sufficient for a direct atomic interpretation. To overcome this, cryo-EM data are often combined with high-resolution atomic structures. However, current computational approaches typically do not include information from other experimental sources nor a proper physico-chemical description of the interfaces. Here we describe the integration of cryo-EM data into our data-driven docking program HADDOCK and its performance on a benchmark of 17 complexes. The approach is demonstrated on five systems using experimental cryo-EM data in the range of 8.5-21 Å resolution. For several cases, cryo-EM data are integrated with additional interface information, e.g. mutagenesis and hydroxyl radical footprinting data. The resulting models have high-quality interfaces, revealing novel details of the interactions.
Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht 3584CH, the Netherlands.
Gydo C P
GCP
van Zundert
Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht 3584CH, the Netherlands.
Adrien S J
ASJ
Melquiond
Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht 3584CH, the Netherlands. Electronic address: a.m.j.j.bonvin@uu.nl.
Alexandre M J J
AMJJ
Bonvin
D019295:Computational Biology / Q000379:methods*; D020285:Cryoelectron Microscopy; D030562:Databases, Protein; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism*; D014584:User-Computer Interface
D046912:Multiprotein Complexes