ADP_EM: fast exhaustive multi-resolution docking for high-throughput coverage

Garzón, José Ignacio; Kovacs, Julio A.; Abagyan, Ruben; Chacón, Pablo

doi:10.1093/bioinformatics/btl625

Cited by 95 publications

(120 citation statements)

References 44 publications

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“…The pairwise structure comparison with 3DZD takes only 1.46x10 -4 s. Simply multiplying this execution time by the current size of PDB (64098 proteins) gives 9.36 seconds, while the same procedure by CE results will need almost 2 days. The speed of 3DZD is significantly faster than previous similar works on EM density map search [11,12]. …”

Section: Resultsmentioning

confidence: 99%

“…Here, challenges include how to use a low-resolution EM density map for fitting high resolution structures [7-9] or guiding protein structure prediction [10], and how to efficiently and accurately compare global and local structures [11,12]. Thus, development of a new generation of structure analysis tools, which allow a fast screening of large structure databases and can handle low resolution structure data, is needed.…”

Section: Introductionmentioning

confidence: 99%

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Improved protein surface comparison and application to low-resolution protein structure data

Sael

2010

BMC Bioinformatics

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BackgroundRecent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics. With the number of known structures of unknown function expanding at a rapid pace, an urgent task is to provide reliable clues to their biological function on a large scale. Conventional approaches for structure comparison are not suitable for a real-time database search due to their slow speed. Moreover, a new challenge has arisen from recent techniques such as electron microscopy (EM), which provide low-resolution structure data. Previously, we have introduced a method for protein surface shape representation using the 3D Zernike descriptors (3DZDs). The 3DZD enables fast structure database searches, taking advantage of its rotation invariance and compact representation. The search results of protein surface represented with the 3DZD has showngood agreement with the existing structure classifications, but some discrepancies were also observed.ResultsThe three new surface representations of backbone atoms, originally devised all-atom-surface representation, and the combination of all-atom surface with the backbone representation are examined. All representations are encoded with the 3DZD. Also, we have investigated the applicability of the 3DZD for searching protein EM density maps of varying resolutions. The surface representations are evaluated on structure retrieval using two existing classifications, SCOP and the CE-based classification.ConclusionsOverall, the 3DZDs representing backbone atoms show better retrieval performance than the original all-atom surface representation. The performance further improved when the two representations are combined. Moreover, we observed that the 3DZD is also powerful in comparing low-resolution structures obtained by electron microscopy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improved protein surface comparison and application to low-resolution protein structure data

Sael

2010

BMC Bioinformatics

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“…We performed a rigid-body fit of C3b (PDB file 2i07) into the EM reconstruction of C3b and the C3bB(Ni 2ϩ ) complex using ADP EM (31). C3b was unambiguously located in the C3bB(Ni 2ϩ ) complex, and a difference map between this fitted C3b and the full map was used to extract the density in the complex assigned to fB.…”

Section: Methodsmentioning

confidence: 99%

3D structure of the C3bB complex provides insights into the activation and regulation of the complement alternative pathway convertase

Torreira

Tortajada

Montes

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Generation of the alternative pathway C3-convertase, the central amplification enzyme of the complement cascade, initiates by the binding of factor B (fB) to C3b to form the proconvertase, C3bB. C3bB is subsequently cleaved by factor D (fD) at a single site in fB, producing Ba and Bb fragments. Ba dissociates from the complex, while Bb remains bound to C3b, forming the active alternative pathway convertase, C3bBb. Using single-particle electron microscopy we have determined the 3-dimensional structures of the C3bB and the C3bBb complexes at Ϸ27Å resolution. The C3bB structure shows that fB undergoes a dramatic conformational change upon binding to C3b. However, the C3b-bound fB structure was easily interpreted after independently fitting the atomic structures of the isolated Bb and Ba fragments. Interestingly, the divalent cationbinding site in the von Willebrand type A domain in Bb faces the C345C domain of C3b, whereas the serine-protease domain of Bb points outwards. The structure also shows that the Ba fragment interacts with C3b separately from Bb at the level of the ␣ NT and CUB domains. Within this conformation, the long and flexible linker between Bb and Ba is likely exposed and accessible for cleavage by fD to form the active convertase, C3bBb. The architecture of the C3bB and C3bBb complexes reveals that C3b could promote cleavage and activation of fB by actively displacing the Ba domain from the von Willebrand type A domain in free fB. These structures provide a structural basis to understand fundamental aspects of the activation and regulation of the alternative pathway C3-convertase.C3 convertase ͉ electron microscopy ͉ factor B

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“…Further optimization of the fit can then be tried using the Fit in Map routines in UCSF Chimera. Many advances have been made in both sensitivity and speed of cross-correlation based rigid body fitting (Bettadapura et al, 2015;Chacón and Wriggers, 2002;Derevyanko and Grudinin, 2014;Farabella et al, 2015;Garzón et al, 2007;Hoang et al, 2013;Hrabe et al, 2012;Roseman, 2000;Volkmann and Hanein, 1999;Volkmann, 2009;Wu et al, 2003). Recently, we introduced the coreweighted local cross-correlation scores in our rigid-body fitting package PowerFit .…”

Section: Introductionmentioning

confidence: 99%

Defining the limits and reliability of rigid-body fitting in cryo-EM maps using multi-scale image pyramids

Zundert

Bonvin

2016

Journal of Structural Biology

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. Defining the limits and reliability of rigid-body fitting in cryo-EM maps using multi-scale image pyramids. J. Struct. Biol., 195, 252-258 (2016).https://doi.org/10. 1016/j.jsb.2016.06.011 Defining the limits and reliability of rigid-body fitting in cryo-EM maps using multi-scale image pyramids Keywords1Cross correlation; PowerFit; Ribosome; Fisher z-transformation; Core-weighted; Modeling. AbstractCryo-electron microscopy provides fascinating structural insight into large macromolecular machines at increasing detail. Despite significant advances in the field, the resolution of the resulting three-dimensional images is still typically insufficient for de novo model building.To bridge the resolution gap and give an atomic interpretation to the data, high-resolution models are typically placed into the density as rigid bodies. Unfortunately, this is often done manually using graphics software, a subjective method that can lead to over-interpretation of the data. A more objective approach is to perform an exhaustive cross-correlation-based search to fit subunits into the density. Here we show, using five experimental ribosome maps ranging in resolution from 5.5 to 6.9Å, that cross-correlation-based fitting is capable of successfully fitting subunits correctly in the density for over 90% of the cases. Importantly, we provide indicators for the reliability and ambiguity of a fit, using the Fisher ztransformation and its associated confidence intervals, giving a formal approach to identify over-interpreted regions in the density. In addition, we quantify the resolution requirement for a successful fit as a function of the subunit size. For larger subunits the resolution of the data can be down-filtered to 20Å while still retaining an unambiguous fit. We leverage this information through the use of multi-scale image pyramids to accelerate the search up to 30-fold on CPUs and 40-fold on GPUs at a negligible loss in success rate. We implemented this approach in our rigid-body fitting software PowerFit, which can be freely downloaded from https://github.com/haddocking/powerfit.

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ADP_EM: fast exhaustive multi-resolution docking for high-throughput coverage

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 95 publications

References 44 publications

Improved protein surface comparison and application to low-resolution protein structure data

Improved protein surface comparison and application to low-resolution protein structure data

3D structure of the C3bB complex provides insights into the activation and regulation of the complement alternative pathway convertase

Defining the limits and reliability of rigid-body fitting in cryo-EM maps using multi-scale image pyramids

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