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. 2010 Nov 15;78(15):3205-11.
doi: 10.1002/prot.22845.

Determining macromolecular assembly structures by molecular docking and fitting into an electron density map

Keren Lasker  1 , Andrej Sali, Haim J Wolfson
Affiliations

Determining macromolecular assembly structures by molecular docking and fitting into an electron density map

Keren Lasker et al. Proteins. .

Abstract

Structural models of macromolecular assemblies are instrumental for gaining a mechanistic understanding of cellular processes. Determining these structures is a major challenge for experimental techniques, such as X-ray crystallography, NMR spectroscopy and electron microscopy (EM). Thus, computational modeling techniques, including molecular docking, are required. The development of most molecular docking methods has so far been focused on modeling of binary complexes. We have recently introduced the MultiFit method for modeling the structure of a multisubunit complex by simultaneously optimizing the fit of the model into an EM density map of the entire complex and the shape complementarity between interacting subunits. Here, we report algorithmic advances of the MultiFit method that result in an efficient and accurate assembly of the input subunits into their density map. The successful predictions and the increasing number of complexes being characterized by EM suggests that the CAPRI challenge could be extended to include docking-based modeling of macromolecular assemblies guided by EM.

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Figures

Figure 1
Figure 1. Outline of the MultiFit protocol for simultaneous fitting
The stages of the MultiFit (left) and the Cn_MultiFit (right) algorithms are illustrated from top to bottom. (left) The input is a density map of the MMO hydroxylase complex simulated to 20 Å resolution (gray) and atomic models of the α, β and γ subunits (colors). Segmentation of the density map into 6 regions (light gray) and the corresponding anchor graph (black) as calculated in the “anchor graph segmentation stage”. An assignment of subunits into regions and an atomic model as sampled in the “fitting-based assembly configuration” stage (colors). A refinement of the model (colors) as sampled in the “docking-based pose refinement” stage fitted to the density map (light gray). The final model (colors) superposed on the native complex (gray). (right) The input is an experimentally determined density map of the GroEL complex at 23.5 Å resolution and an atomic structure of the monomeric subunit. The predicted symmetry axis (red) as calculated in the “symmetry axis detection” stage. Segmentation of the density map into 7 regions (light gray) and the corresponding anchor graph (black). A models sampled in the “fitting-based Cn assembly configuration” stage (colors) fitting to the density map (light gray). The final model (colors) superposed on the native complex (gray).
Figure 2
Figure 2. Benchmark results
Final models (colors) for 6 of the benchmark cases. For each test case the PDB entry code, the number of subunits and the final Cα-RMSD to the native structure are listed.
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References

    1. Alberts B. The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell. 1998;92(3):291–294. - PubMed
    1. Robinson CV, Sali A, Baumeister W. Molecular sociology of the cell. Nature. 2007;450:973–982. - PubMed
    1. Sali A, Glaeser R, Earnest T, Baumeister W. From words to literature in structural proteomics. Nature. 2003;422(6928):216–225. - PubMed
    1. Alber F, Forster F, Korkin D, Topf M, Sali A. Integrating diverse data for structure determination of macromolecular assemblies. Annu Rev Biochem. 2008;77:443–477. - PubMed
    1. Pons C, Grosdidier S, Solernou A, Perez-Cano L, Fernandez-Recio J. Present and future challenges and limitations in protein-protein docking. Proteins. 78(1):95–108. - PubMed

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