Mass Spec Studio for Integrative Structural Biology

Rey, Martial; Sarpe, Vladimir; Burns, Kyle M.; Buse, Joshua; Baker, Charles A.; Dijk, Marc van; Wordeman, Linda; Bonvin, Alexandre M. J. J.; Schriemer, David C.

doi:10.1016/j.str.2014.08.013

Cited by 93 publications

(97 citation statements)

References 54 publications

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“…LC-MS/MS data was processed with the covalent labeling plug-in in Mass Spec Studio for tracking modified peptides [40]. The cross-linking Mass Spec Studio plug-in was used for peptide identification, as it incorporates probabilistic scoring methodology for singly-labeled (so-called Bdead-end^) peptides [41].…”

Section: Discussionmentioning

confidence: 99%

Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

Ziemianowicz

Bomgarden

Etienne

et al. 2017

J. Am. Soc. Mass Spectrom.

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Abstract. Mapping proteins with chemical reagents and mass spectrometry can generate a measure of accessible surface area, which in turn can be used to support the modeling and refinement of protein structures. Photolytically generated carbenes are a promising class of reagent for this purpose. Substituent effects appear to influence surface mapping properties, allowing for a useful measure of design control. However, to use carbene labeling data in a quantitative manner for modeling activities, we require a better understanding of their inherent amino acid reactivity, so that incorporation data can be normalized. The current study presents an analysis of the amino acid insertion frequency of aliphatic carbenes generated by the photolysis of three different diazirines: 3,3'-azibutyl-1-ammonium, 3,3'-azibutan-1-ol, and 4,4'-azipentan-1-oate. Leveraging an improved photolysis system for single-shot labeling of sub-microliter frozen samples, we used EThCD to localize insertion products in a large population of labeled peptides. Counting statistics were drawn from data-dependent LC-MS 2 experiments and used to estimate the frequencies of insertion as a function of amino acid. We observed labeling of all 20 amino acids over a remarkably narrow range of insertion frequencies. However, the nature of the substituent could influence relative insertion frequencies, within a general preference for larger polar amino acids. We confirm a large (6-fold) increase in labeling yield when carbenes were photogenerated in the solid phase (77 K) relative to the liquid phase (293 K), and we suggest that carbene labeling should always be conducted in the frozen state to avoid information loss in surface mapping experiments.

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Section: Discussionmentioning

confidence: 99%

Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

Ziemianowicz

Bomgarden

Etienne

et al. 2017

J. Am. Soc. Mass Spectrom.

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“…Informationdriven methods address this issue by utilizing experimental restraints to better define the overall search space and reduce the range of outputted decoys. [19,20] HDX-MS difference plots allow the identification of residues residing in protein-protein interfaces which can then be activated prior to protein docking. However, this binary implementation of HDX-MS restraints only allows residues to be switched into on/off positions and overlooks the overall shape of the experimental difference profile.…”

Section: Simulated Isotope Exchange Patterns Enable Protein Structurementioning

confidence: 99%

Simulated Isotope Exchange Patterns Enable Protein Structure Determination

Borysik

2017

Angew Chem Int Ed

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Understanding the myriad protein–protein interactions required for cell function requires efficient leveraging of biophysical data to drive computational docking. The detailed insight into protein interfaces provided by isotope exchange endows this experimental technique with a unique importance for docking approaches. However, progress in coupling these methods is hindered by the inability to interpret the complex exchange patterns in relation to protein structure. A method to simulate protein isotope exchange patterns from docking outputs is described and its utility to guide the selection of native assemblies demonstrated. Unique signatures are generated for each docking pose, allowing high‐throughput ranking of whole docking simulations by pairwise comparison to experimental outputs. Native assemblies are obtained using nothing but their simulated profiles as restraints and experimental difference data for individual proteins are sufficient to drive structure determination for the whole complex.

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“…Analysis of Volumes in Structural Biology: Finally, we may try to recognize secondary structure elements [87]- [89], we may identify components by constraining the identification with other experimental sources like mass spectroscopy [90] and proteomics and chemical cross-linking [91], we may add a priori knowledge about atomic models that should fit into the 3D reconstruction [92]- [96], or analyze its possible deformation paths [97], [98].…”

Section: ) High-resolution Electron Imaging: Direct Detection Devicementioning

confidence: 99%

A Guided Tour of Selected Image Processing and Analysis Methods for Fluorescence and Electron Microscopy

Kervrann

Sorzano

Acton

et al. 2016

IEEE J. Sel. Top. Signal Process.

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Abstract-Microscopy imaging, including fluorescence microscopy and electron microscopy, has taken a prominent role in life science research and medicine due to its ability to investigate the 3D interior of live cells and organisms. A long-term research in bio-imaging at the sub-cellular and cellular scales consists then in inferring the relationships between the dynamics of macromolecules and their functions. In this area, image processing and analysis methods are now essential to understand the dynamic organization of groups of interacting molecules inside molecular machineries and to address issues in fundamental biology driven by advances in molecular biology, optics and technology. In this paper, we present recent advances in fluorescence and electron microscopy and we focus on dedicated image processing and analysis methods required to quantify phenotypes for a limited number but typical studies in cell imaging.

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Mass Spec Studio for Integrative Structural Biology

Cited by 93 publications

References 54 publications

Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

Simulated Isotope Exchange Patterns Enable Protein Structure Determination

A Guided Tour of Selected Image Processing and Analysis Methods for Fluorescence and Electron Microscopy

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