Prediction of Multimolecular Assemblies by Multiple Docking

Inbar, Yuval; Benyamini, Hadar; Nussinov, Ruth; Wolfson, Haim J.

doi:10.1016/j.jmb.2005.03.039

Cited by 81 publications

(67 citation statements)

References 52 publications

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“…In this approach, one can use computational docking methods (Pierce et al, 2005;Schneidman-Duhovny et al, 2005a,b;Karaca et al, 2010;Inbar et al, 2005;Kuzu et al, 2014) to first construct a large number of protein-assembly models by exploiting existing highresolution structural information from X-ray crystallography and NMR spectroscopy. Using this as a basis set, it is possible to use lower resolution 3DEM density maps to evaluate, rank and select the best models that are both structurally plausible and consistent with the experimental density maps.…”

Section: Introductionmentioning

confidence: 99%

PRISM-EM: template interface-based modelling of multi-protein complexes guided by cryo-electron microscopy density maps

Kuzu

Keskin

Nussinov

et al. 2016

Acta Cryst Sect D Struct Biol

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The structures of protein assemblies are important for elucidating cellular processes at the molecular level. Three-dimensional electron microscopy (3DEM) is a powerful method to identify the structures of assemblies, especially those that are challenging to study by crystallography. Here, a new approach, PRISM-EM, is reported to computationally generate plausible structural models using a procedure that combines crystallographic structures and density maps obtained from 3DEM. The predictions are validated against seven available structurally different crystallographic complexes. The models display mean deviations in the backbone of <5 Å . PRISM-EM was further tested on different benchmark sets; the accuracy was evaluated with respect to the structure of the complex, and the correlation with EM density maps and interface predictions were evaluated and compared with those obtained using other methods. PRISM-EM was then used to predict the structure of the ternary complex of the HIV-1 envelope glycoprotein trimer, the ligand CD4 and the neutralizing protein m36.

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Section: Introductionmentioning

confidence: 99%

PRISM-EM: template interface-based modelling of multi-protein complexes guided by cryo-electron microscopy density maps

Kuzu

Keskin

Nussinov

et al. 2016

Acta Cryst Sect D Struct Biol

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“…Such a situation is also encountered in hierarchical folding strategies (75,76), as discussed for CombDock (41), which also suffers from this handicap. Another problem is choosing the right prediction.…”

Section: Discussionmentioning

confidence: 97%

“…However, expensive computation of the ab initio docking is a barrier for large-scale protein complex predictions. Computationally, modeling of multimolecular assemblies from the structures of their monomeric components is challenging because of the large number of possible combinations of the components (41).…”

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confidence: 99%

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Modeling Protein Assemblies in the Proteome

Kuzu

Keskin

Nussinov

et al. 2014

Molecular & Cellular Proteomics

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Most (if not all) proteins function when associated in multimolecular assemblies. Attaining the structures of protein assemblies at the atomic scale is an important aim of structural biology. Experimentally, structures are increasingly available, and computations can help bridge the resolution gap between high-and low-resolution scales. Existing computational methods have made substantial progress toward this aim; however, current approaches are still limited. Some involve manual adjustment of experimental data; some are automated docking methods, which are computationally expensive and not applicable to large-scale proteome studies; and still others exploit the symmetry of the complexes and thus are not applicable to nonsymmetrical complexes. Our study aims to take steps toward overcoming these limitations. We have developed a strategy for the construction of protein assemblies computationally based on binary interactions predicted by a motif-based protein interaction prediction tool, PRISM (Protein Interactions by Structural Matching). Previously, we have shown its power in predicting pairwise interactions. Here we take a step toward multimolecular assemblies, reflecting the more prevalent cellular scenarios. With this method we are able to construct homo-/ hetero-complexes and symmetric/asymmetric complexes without a limitation on the number of components. The method considers conformational changes and is applicable to large-scale studies. We also exploit electron microscopy density maps to select a solution from among the predictions. Here we present the method, illustrate its results, and highlight its current limitations. Molecular &

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“…The strength of this approach is derived from the decomposition procedure, which helps to reduce the size of the search space from exponential in the number of components in the whole system to exponential in the number of components in the largest subset. Similar ideas have been used for various modeling tasks such as side chain packing (102-104), sequence-structure threading (103), ab initio RNA folding (105), and prediction of quaternary structures of multiprotein complexes (106).…”

Section: Divide-and-conquer Optimizersmentioning

confidence: 99%