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this presentation is about Hydrogen Deuterium Exchange mass spectrometry
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HDX-MS Activities M.ABBASSI
Content Layout • Hydrogen- Deuterium Exchange Mass Spectrometry (HDX-MS) in drug discovery • Groups search and activate in this field
Hydrogen- Deuterium Exchange Mass Spectrometry (HDX-MS) in drug discovery Hydrogen deuterium exchange mass spectrometry (HDX-MS) is rapidly becoming an important part of the biochemist’s toolkit for exploring protein structure, dynamics, and function. • Study protein folding • Study protein oligomerization • protein:protein interactions • protein:DNA interactions • protein: small molecule interactions • protein: membrane interactions complement orthogonal biophysical techniques such as X-ray crystallography, nuclear magnetic resonance and electron microscopy
HDX-MS methodology • Deuterium incorporation • Spatial localization of deuterium incorporation • Bottom-up HDX-MS approaches • Top down HDX-MS approaches
Theoretical underpinnings of amide deuteriumexchange Backbone amides engaged in secondary structure exchange with solvent via the following mechanism.
Teams in this Field • K. Rand (Copenhagen University) • J. Bruke ( University of Victoria) • A. Politis (King's College London) • Griffin, P.R. (Scripps Florida) • Chen. G (Bristol-Myers Squibb)
University of Copenhagen Rand, Kasper Dyrberg
Rand, Kasper Dyrberg Position: Group Leader, Protein Analysis Lab, Dept. of Pharmacy, University of Copenhagen Research Interests: Bioanalytical Chemistry & Protein Analytical Chemistry Analysis of the primary structure of proteins by liquid chromatography and mass spectrometry Analysis of the higher-order structure and molecular interactions of proteins of pharmaceutical interest by hydrogen/deuterium exchange mass spectrometry (HDX-MS) Quantitative analysis of proteins by mass spectrometry-based methods Research Supervision Main supervisor of PhD students: Patrick Merkle, Ingvar Møller, ZeinabNasari, EsbenTrabjerg, UlrikMistarz Main supervisor of >10 Master thesis students Supervisor of Postdocs: PernilleFoged Jensen and Signe Seger Supervisor of Assistant Professor: Tam T.T Nguyen
Article • Funder: Det Frie Det Frie Forskningsråd Grant: Sapere Aude Grant / DFF-4184-00537A
THE UNIVERSITY of VICTORIA John E Burke Lab.
New Article J.E.B. is supported by a new investigator grant from CIHR, a discovery research grant from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2020-04241), and a Michael Smith Foundation for Health Research (MSFHR)Scholar award (17686). We appreciate feedback from members of the Burke lab during preparation.
King’s College London Dr. Politis, Argyris
DrArgyrisPolitis • Senior Lecturer in Chemical Systems Biology (GTA Lead. Year 3 Lead.) • Research subject areas: Chemistry Research Interests: • Understanding, describing and modulating many of the cells’ functions requires structure characterization of its macromolecular assemblies. However, the study of many heterogeneous assemblies by traditional methods remains challenging, thus impeding structural information of important biological machines. Hybrid structural biology approaches, which combine information from various sources, can address this challenge enabling insights for systems that remain elusive by a single method. • DrPolitis' group develops and applies computational and experimental methods to study the structure and function of protein assemblies. Specifically, they aim to: • a) develop hybrid structural biology methods to predict the structure of large protein complexes, • b) perform mass spectrometry based experiments to generate structural restraints for capturing the flexibility and assembly pathways of transient complexes, • c) use the structural predictions to develop testable hypotheses for annotating the functions of biologically important proteins such as membrane embedded proteins and those involved in cell cycle
Projects • Mechanism of Membrane Transporters • Nucleic Acid Binding Proteins • Mechanism of multi-drug efflux pump using hybrid-MS methodology • Antibody structure and function • Integrative modelling • Modelling of Membrane Proteins • Modelling of Soluble Macromolecular Assemblies