Inherent limitations in protein–protein docking procedures

Kowalsman, Noga; Eisenstein, Miriam

doi:10.1093/bioinformatics/btl524

Cited by 26 publications

(25 citation statements)

References 20 publications

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“…There is evidence that the raw scores provided by docking methods often show a poor correlation with the probabilities of a given solution to be correct and, perhaps more importantly, these scores are not comparable between experiments involving different molecules, since they are very much dependent on the size and shape of the molecules tested [56]. However, given that we are benchmarking state-of-the-art methods on a large set of protein interactions, and that we need to drastically reduce the number of solutions to be included in the 3D-Repertoire modelling pipeline, we decided to explore the possibility of increasing the accuracy of the results by identifying a general score threshold, at expenses of reducing the coverage.…”

Section: Resultsmentioning

confidence: 99%

Pushing Structural Information into the Yeast Interactome by High-Throughput Protein Docking Experiments

Mosca

Pons²,

Fernández‐Recio

et al. 2009

PLoS Comput Biol

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The last several years have seen the consolidation of high-throughput proteomics initiatives to identify and characterize protein interactions and macromolecular complexes in model organisms. In particular, more that 10,000 high-confidence protein-protein interactions have been described between the roughly 6,000 proteins encoded in the budding yeast genome (Saccharomyces cerevisiae). However, unfortunately, high-resolution three-dimensional structures are only available for less than one hundred of these interacting pairs. Here, we expand this structural information on yeast protein interactions by running the first-ever high-throughput docking experiment with some of the best state-of-the-art methodologies, according to our benchmarks. To increase the coverage of the interaction space, we also explore the possibility of using homology models of varying quality in the docking experiments, instead of experimental structures, and assess how it would affect the global performance of the methods. In total, we have applied the docking procedure to 217 experimental structures and 1,023 homology models, providing putative structural models for over 3,000 protein-protein interactions in the yeast interactome. Finally, we analyze in detail the structural models obtained for the interaction between SAM1-anthranilate synthase complex and the MET30-RNA polymerase III to illustrate how our predictions can be straightforwardly used by the scientific community. The results of our experiment will be integrated into the general 3D-Repertoire pipeline, a European initiative to solve the structures of as many as possible protein complexes in yeast at the best possible resolution. All docking results are available at http://gatealoy.pcb.ub.es/HT_docking/.

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Section: Resultsmentioning

confidence: 99%

Pushing Structural Information into the Yeast Interactome by High-Throughput Protein Docking Experiments

Mosca

Pons²,

Fernández‐Recio

et al. 2009

PLoS Comput Biol

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“…Therefore, standard scan intervals of 12°and 1.05 Å were used in all of the scans. Statistical analysis of the docking scores was executed by fitting an extreme value distribution function to the distribution of scores (37). The fit provided estimates of the mean score, ϭ 525, and the S.D., ϭ 90.…”

Section: Mutationsmentioning

confidence: 99%

Molecular Mechanisms and Kinetic Effects of FXYD1 and Phosphomimetic Mutants on Purified Human Na,K-ATPase

Mishra

Habeck

Kirchner

et al. 2015

Journal of Biological Chemistry

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“…Several symmetry related correct matches were ranked at the top followed by a false match (ranked 5) in which the tip of GroES makes contact with the central void of the GroEL trans ring. Fitting of an extreme value distribution function to the distribution of scores [35] provided estimated E values of 5.6×10 −4 and 2.1×10 −3 , respectively, for the highest ranking correct and false models.…”

Section: Resultsmentioning

confidence: 99%

FitEM2EM—Tools for Low Resolution Study of Macromolecular Assembly and Dynamics

Frankenstein

Sperling

et al. 2008

PLoS ONE

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Studies of the structure and dynamics of macromolecular assemblies often involve comparison of low resolution models obtained using different techniques such as electron microscopy or atomic force microscopy. We present new computational tools for comparing (matching) and docking of low resolution structures, based on shape complementarity. The matched or docked objects are represented by three dimensional grids where the value of each grid point depends on its position with regard to the interior, surface or exterior of the object. The grids are correlated using fast Fourier transformations producing either matches of related objects or docking models depending on the details of the grid representations. The procedures incorporate thickening and smoothing of the surfaces of the objects which effectively compensates for differences in the resolution of the matched/docked objects, circumventing the need for resolution modification. The presented matching tool FitEM2EMin successfully fitted electron microscopy structures obtained at different resolutions, different conformers of the same structure and partial structures, ranking correct matches at the top in every case. The differences between the grid representations of the matched objects can be used to study conformation differences or to characterize the size and shape of substructures. The presented low-to-low docking tool FitEM2EMout ranked the expected models at the top.

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Inherent limitations in protein–protein docking procedures

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 26 publications

References 20 publications

Pushing Structural Information into the Yeast Interactome by High-Throughput Protein Docking Experiments

Pushing Structural Information into the Yeast Interactome by High-Throughput Protein Docking Experiments

Molecular Mechanisms and Kinetic Effects of FXYD1 and Phosphomimetic Mutants on Purified Human Na,K-ATPase

FitEM2EM—Tools for Low Resolution Study of Macromolecular Assembly and Dynamics

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