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More mass spectrometry books

reviewed by T. Nelson


Hydrogen Exchange Mass Spectrometry of Proteins: Fundamentals, Methods, and Applications
by David D. Weis, ed.

Wiley, 2016, 350 pages

Reviewed by T. Nelson

H ydrogen-deuterium exchange mass spectrometry, or HX for short, is a new technique for studying the structure or function of a protein and for identifying epitopes involved in ligand binding and protein-protein interactions. Although it's not terribly difficult for someone with lots of protein mass spec experience, there are many pitfalls that can be missed when looking at review papers and such.

That's why a book like this was badly needed. To my knowledge, this is the first one ever published on this subject. Many of the authors of these 18 chapters are well known experts. A beginner will benefit from their experience and from becoming familiar with the potential problems, of which there are many.

In HX, you mix your protein with D2O to replace the hydrogens with deuteriums. Then you remove the D2O and add water, chop the protein into small peptides, and throw it on the mass spectrometer. This tells you where the deuterium is on the protein; if some part of the protein is exposed on the surface, the deuterium will be replaced by hydrogen faster.

One problem is H/D scrambling in collision-induced dissociation, or CID (you can probably see by now why we use all those acronyms). CID causes H and D to be scrambled in MS/MS spectra, greatly limiting the resolution. New ionization types, notably electron capture dissociation (ECD) and electron transfer dissociation (ETD) will help (if you can afford them).

Still, the multi-author format means there's a certain amount of repetition. HX is just a technique, but there are few nitty-gritty details: no pictures of the equipment, no detailed algorithms, and not much statistical analysis. There are also no step-by-step protocols, no comparisons of different techniques or different instruments, mass spec settings, or columns, and no background on interpreting spectra for anyone unfamiliar with that.

This makes sense: someone just starting out with protein mass spec has a big enough learning curve already. This book will get you oriented to the new technique, maybe give you an idea of what you could use it for, and point you to the software you'll need. Take my word for it: you don't want to calculate these things by hand.

It's pretty biophysics-oriented, so there are lots of discussions of kinetics and some structural biochemistry. Mostly you'll find specific examples of how the technique was used in the authors' own experiments. So, while this book will be interesting to those (like me) who are planning to use the technique, my advice to the general reader is: stay away. Stay far, far away.

jul 01, 2017; edited jul 04, 2017