Article
Biochemical Research Methods
Bradley B. Stocks, Gregory H. Bird, Loren D. Walensky, Jeremy E. Melanson
Summary: The number of approved peptide therapeutics and those in development is increasing. The biological activity of therapeutic peptides is often influenced by their structural elements, with stabilizing features improving bioavailability. The use of hydrocarbon stapling can dramatically stabilize alpha-helical peptides. Mass spectrometry techniques like IM and HDX can detect multiple peptide conformations, aiding in the identification of optimally stapled peptides.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Review
Chemistry, Multidisciplinary
Rebecca Beveridge, Antonio N. Calabrese
Summary: Intrinsically disordered proteins and regions of intrinsic disorder play crucial roles in biological processes by overcoming binding restrictions and enhancing binding specificity. Structural mass spectrometry methods are increasingly important for studying these proteins, providing new insights into their structure and function. Their flexibility and advantages make them ideal tools for understanding intrinsically disordered proteins.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Analytical
Joseph Anacleto, Cristina Lento, Vladimir Sarpe, Ayesha Maqsood, Banafsheh Mehrazma, David Schriemer, Derek J. Wilson
Summary: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a rapidly growing technique that provides information about the dynamic structural changes in proteins during biological function. The continuous flow injection setup for time-resolved HDX-MS (CFI-TRESI-HDX) introduced in this work allows for automated, continuous or discrete labeling time measurements from milliseconds to hours, with substantially reduced runtimes compared to conventional systems.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Eric Largy, Matthieu Ranz
Summary: Hydrogen-deuterium exchange mass spectrometry (HDX/MS) is used for studying protein conformation dynamics and characterizing oligonucleotide conformations and their interactions with cations, small molecules, and proteins. OligoR is a web-based application that provides dedicated solutions for processing and visualizing native HDX/MS data of oligonucleotides. It offers a simple and robust approach to deconvoluting bimodal isotope distributions and can be extended to various analytes. The results are presented in interactive data tables and can be exported as publication-quality figures.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Ramin Ekhteiari Salmas, Antoni James Borysik
Summary: The quantification of hydrogen deuterium exchange (HDX) kinetics provides information on the stability of individual amino acids in proteins. The new programming tool HDXmodeller allows for optimization of low-resolution HDX-mass spectrometry (MS) data to understand exchange rates of individual amino acids. The tool also has a unique autovalidation method based on a covariance matrix for quantifying the accuracy of modeled exchange rates.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Haley M. M. Schramm, Tomoya Tamadate, Christopher J. J. Hogan, Brian H. H. Clowers
Summary: The rates and mechanisms of chemical reactions at phase boundaries are different from those in bulk solution, but are difficult to quantify. Ion-neutral interactions play critical roles in aerosol formation, atmospheric chemistry, and gas-phase ion separations, and their behavior during the early stages of solvation differs from bulk solution. By quantifying the degree of hydrogen-deuterium exchange (HDX) and ion-neutral clustering through a gas-phase ion separation technique, we found that cluster formation cannot be ignored when modeling complex nucleation processes and biopolymer structural dynamics.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Analytical
Josiah J. Rensner, Young Jin Lee
Summary: This study developed a highly efficient hydrogen-deuterium exchange technique for more accurate metabolite identification in MALDI-MS imaging, while retaining spatial information. By combining deuterium-labeled matrix and D2O vapor, an HDX efficiency of 73-85% was achieved. This method can systematically improve untargeted metabolite annotation through METASPACE annotation.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Applied
Minna Juvonen, Edwin Bakx, Henk Schols, Maija Tenkanen
Summary: This study investigated the potential of using TWIMS and CID-TWIMS-MS/MS to separate cereal-derived isomeric arabinoxylanoligosaccharides (A)XOS. The triand pentasaccharide isomers were distinguishable by the ATDs of the precursor ions, while CID-TWIMS-MS/MS could effectively separate isomeric fragment ions produced from tetra- and pentasaccharide (A)XOS. The base peak mobility spectrum was also introduced as a practical tool for (A)XOS fingerprinting.
Article
Biochemical Research Methods
Yoshitomo Hamuro, Stephen J. Coales
Summary: This note discusses the challenges and considerations of observing perturbation of a protein upon binding to a ligand with weak affinity using HDX-MS. The theoretical analysis suggests that the ratio of ligand concentration to dissociation constant can greatly impact the results of the experiment.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Biochemistry & Molecular Biology
Helen T. Hobbs, Neel H. Shah, Jean M. Badroos, Christine L. Gee, Susan Marqusee, John Kuriyan
Summary: The catalytic activity of Syk-family tyrosine kinases is regulated by a tandem Src homology 2 module, which differs in conformational dynamics from ZAP-70, impacting the stability of its autoinhibited state and potentially influencing downstream signaling pathways in T cells.
Article
Biochemistry & Molecular Biology
Jarrod J. Sandow, Iris Kl Tan, Alan S. Huang, Shashank Masaldan, Jonathan P. Bernardini, Ahmad Z. Wardak, Richard W. Birkinshaw, Robert L. Ninnis, Ziyan Liu, Destiny Dalseno, Daisy Lio, Giuseppi Infusini, Peter E. Czabotar, Andrew Webb, Grant Dewson
Summary: In this study, the dynamic structural mechanisms of BAK activation on a membrane were explored using HDX-MS. It was found that the BH4 domain maintains the inactive conformation of BAK, and the N-terminal region becomes disordered post-activation without affecting its membrane permeabilization. These findings provide new insights into the potential therapeutic targeting opportunities for BAK activation.
Article
Biochemical Research Methods
Didier Devaurs, Dinler A. Antunes, Antoni J. Borysik
Summary: Despite being used for several decades in structural studies of molecules, hydrogen-exchange monitoring data are often only qualitatively assessed in computational modeling. Various paradigms and prediction models have been proposed to link molecular structure and hydrogen exchange, but none have been widely accepted by the structural biology community. This paper aims to provide an exhaustive list of these models and hopes to guide research towards the development of better prediction models for improving synergies between hydrogen-exchange monitoring and molecular modeling.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Chemistry, Applied
Hannah J. Mckerchar, Cristina Lento, Rachel Z. Bennie, Jennifer M. Crowther, Fabian Dolamore, Jolon M. Dyer, Stefan Clerens, Davide Mercadante, Derek J. Wilson, Renwick C. J. Dobson
Summary: The properties of milk proteins vary between different mammalian species. This study focuses on comparing the dynamics of beta-lactoglobulin (β lg) proteins from goat and cow milk at different pH levels. The dimeric states of the cow β lg B variant homologue exhibit more conformational flexibility than the goat β lg at lower pH, as observed through hydrogen/deuterium exchange experiments and molecular dynamics simulations. Understanding these dynamic differences in β lg homologues is crucial for understanding the variations in milk processing, human digestion, and immunogenicity.
Article
Biochemical Research Methods
Yoshitomo Hamuro
Summary: In order to make a quantitative argument for a hydrogen/deuterium exchange-mass spectrometry (HDX-MS) experiment, optimization at different stages and extraction of relevant values from medium-resolution data is necessary, while being cautious of potential false results.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Biochemistry & Molecular Biology
Edward A. Dennis
Summary: Lipids play important roles in chronic diseases, but defining the substrate specificity of lipid metabolism enzymes is challenging. This research focuses on how membranes interact with enzymes to regulate cell signaling and metabolic pathways. By using substrate lipidomics and molecular dynamics simulations, the study reveals the link between enzyme specificity and hydrophobic binding subsites for membrane phospholipid substrates.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
James R. Arndt, Samaneh Ghassabi Kondalaji, Megan M. Maurer, Arlo Parker, Justin Legleiter, Stephen J. Valentine
Article
Biochemical Research Methods
Mahdiar Khakinejad, Samaneh Ghassabi Kondalaji, Amirmahdi Tafreshian, Stephen J. Valentine
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2015)
Article
Energy & Fuels
Hossein Maleki, Samaneh Ghassabi Kondalaji, Mandiar Khakinejad, Stephen J. Valentine
Article
Biochemical Research Methods
Mahdiar Khakinejad, Samaneh Ghassabi Kondalaji, Gregory C. Donohoe, Stephen J. Valentine
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2016)
Article
Biochemical Research Methods
Samaneh Ghassabi Kondalaji, Mahdiar Khakinejad, Amirmahdi Tafreshian, Stephen J. Valentine
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2017)
Article
Biochemical Research Methods
Mahdiar Khakinejad, Samaneh Ghassabi Kondalaji, Amirmahdi Tafreshian, Stephen J. Valentine
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2017)
Article
Biochemical Research Methods
Samaneh Ghassabi Kondalaji, Mahdiar Khakinejad, Stephen J. Valentine
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2018)
Article
Biochemical Research Methods
Mahdiar Khakinejad, Samaneh Ghassabi Kondalaji, Hossein Maleki, James R. Arndt, Gregory C. Donohoe, Stephen J. Valentine
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2014)