HDX-MS Resources: People, Programs, Papers, PRIDE

Last Updated 28/10/24

Here is a non-exhaustive list of programs, people, papers, and PRIDE datasets that are especially useful.

Presentations

BMSS SIG HDX-MS Theory and Limitations Presentation here

BMSS SIG HDX-MS on the Waters cyclic IMS with Robot here

Papers 

  • Simple and Fast Maximally Deuterated Control (maxD) Preparation for Hydrogen–Deuterium Exchange Mass Spectrometry Experiments Daniele Peterle, Thomas E. Wales, John R. Engen https://pubs.acs.org/doi/10.1021/acs.analchem.2c01446
    • This is the protocol we use for Max D controls generation.
  • Optimization of Feasibility Stage for Hydrogen/Deuterium Exchange Mass Spectrometry Yoshitomo Hamuro, Stephen J. Coales Journal of The American Society for Mass Spectrometry March 2018, Volume 29, Issue 3, pp 623–629
    • Table 1 Quench Conditions provides useful research for initial probing of quench conditions. 
    • Addition of 0.1% of Fos-choline-12 to quench to reduce carryover.
    • Addition of n-octyl-β-D-glucopyranoside to pepsin wash buffer.
    • Elimination of pepsin-rule inconsistent peptides (e.g. pepsin does not cleave proteins after arginine, histidine, lysine, proline, or one residue after proline – so remove them from search criteria). See PEPSIN-WARNING script below for help here!
  • Optimized Workflow for Selecting Peptides for HDX-MS Data Analyses.Sørensen L, Salbo R .J Am Soc Mass Spectrom. 2018 Nov;29(11):2278-2281. doi: 10.1007/s13361-018-2056-1. Epub 2018 Aug 31.
    • Excellent paper that basically states what the best settings are for DynamX when filtering peptides. I would recommend reading the paper in its entirety but the upshot is:
      • Precursor Intensity (minimum intensity): 1481
      • Minimum products per amino acid: 0.11
      • minimum score*: 6.62
      • minimum consecutive products: 1
      • * = the scorse referred to in the DynamX import window is the PLGS score. 
  • Tutorial: Chemistry of Hydrogen/Deuterium Exchange Mass Spectrometry https://pubs.acs.org/doi/10.1021/jasms.0c00260 by Yoshitomo Hamuro. Excellent primer to HDX-MS theory
  • Konermann L, Scrosati PM. Hydrogen/Deuterium Exchange Mass Spectrometry: Fundamentals, Limitations, and Opportunities. Mol Cell Proteomics. 2024 Oct 7:100853. doi: 10.1016/j.mcpro.2024.100853. Very good recent overview of current limitations and problems with the field.

Programs

From Spectra to Deuteration Analysis Programs:

  • Deuteros – FREE. Actively Updated. 
  • HDExaminer – $$ – Free trials available. Actively updated. 
  • DynamX – $$ – Waters instruments ONLY. Last updated 2015. Known bugs.
  • Mass Spec Studio – Free – Supports integration with other mass spec methods. Actively updated. 
  • HaDeX – Free – Extremely useful. Web-based portal for data analysis and post-processing. Makes nice pretty stats, coverage plots and HDX Data Summary tables.

Addons:

ArchaeopteryX by Glenn Masson & Roger Williams. ArchaeopteryX is a user-friendly GUI-based python addon-program that takes DynamX .csv state file outputs and makes them interpretable, along with some basic archiving tools also. It aims to make it possible to fulfil the presentation criteria set out in any future HDX standard paper.  Exports them as .xlsx files. This is very much a work in progress – add to it, chop it up, do what you will with it and let me know! This is an alpha version. The beta version, BaryonyX, which will add some features will be available in September time. Future releases will follow the same pattern (CaudipteryX, DracoreX, EpidexipteryX etc.). Future features will be Redundancy/Coverage scores and pymol painting generators. We realise that many other programs can do this better, but this program is a way to help DynamX users specifically with their data. 

HaDeX: HaDeX very nice web-based subsequent data analysis and visualisation tool – needs DynamX based output data as an input!

Pepsin-Warning: by Lars Soerensen. Pepsin-Warning is a little script that helps you to eliminate peptides that violate pepsin digestion rules.

LARS: Another one from all around great-guy Lars Soerensen: LARS (Listing of Analytically Relevant Sequences) . This program makes identifying peptides to import into DynamX smarter and more streamlined. DynamX often trips-over and does dumb stuff around averaging retention times. For example, let’s say that you have 4 non-deuterated files where the peptide is identifed at 1 minute RT, and one, incorrectly identified at 15 minutes. DynamX will average your retention time to 4 minutes 45 seconds, and it won’t find your peptide, rather than guessing that the 15 min ID is incorrect. This program corrects for that. 

MEMHDX by Stevenn Volant & Veronique Hourdel. DynamX doesn’t have any statistical method for results analysis. MEMHDX aims to rectify this and can identify statistically valid results. It’s a web-based interface – all you need is your .csv output file for it to work.  It’s very intuitive and powerful, but last time I checked you need all your peptides to have data from a single charge state. Also provides much clearer ways of presenting data than uninterpretable butterfly plots. 

HDXsite: https://hdxsite.nms.kcl.ac.uk/ Run by Antoni Borysik at King’s College, London.

People

Academic labs that work with/on HDX-MS. If you wish to be added/removed from this list let me know.

** = Those who have a special interest in method development.

PRIDE Datasets

Here are a list of my HDX-MS PRIDE Archived datasets

Ribsomal/GCN2 Dataset

Raptor/Rags Dataset

PI3Kalpha/Activators/Inhibitors Dataset