Applications of hydrogen/deuterium exchange MS from 2012 to 2014.

Abstract

Hydrogen/deuterium exchange (HDX) detected by mass spectrometry (MS) is extraordinarily useful in the study of many aspects of proteins, especially the analysis of protein conformation and dynamics. While once a challenging and therefore sparingly used method, modern HDX MS is more straightforward, rapid, and routine than in the past. As a result, the breadth of applications of the method has expanded. This Review catalogs applications of HDX MS that have appeared in the literature during the 30 months from January 2012 to June 2014. As penetration of the method into nonacademic sectors where confidentiality is necessary is also at an all-time high, many more applications of this method likely exist that have not been reported in the literature. A synopsis of the recent applications of HDX MS is shown in Figure ​Figure11 where classifications have been made in terms of sector in which the work was performed, geography, and general topic. We elected to categorize the publications in these ways to emphasize that the method is used not only in all sectors but also on nearly every continent. Many different possibilities existed for characterizing the applications by topic, and this was not a perfect task. Some papers belong in multiple topics or could arguably be placed in different categories than we finally decided. An Excel database and an Endnote library of the 234 articles we surveyed, both of which contain the topic groupings, are available from the authors. Figure 1 Synopsis of the published applications of HDX MS from January 2012 to June 2014. (A) A total of two-hundred thirty-four (234) articles were published and classified according to the scheme shown, based on author affiliations. The number of articles in ... Academia is the largest sector contributing to published HDX MS applications (Figure ​(Figure1).1). Approximately 25% of the papers surveyed included multiple sectors, which we have classified as mixed. As mentioned above, such categorization is biased against work that has not been published. Industrial research and research from governmental laboratories must/may remain confidential. Therefore, the results in Figure ​Figure1A1A are to be interpreted with this in mind. The United States was the primary source of publications in HDX MS during the January 2012 to June 2014 time period (Figure ​(Figure1B,C),1B,C), although significant and important work originated from 22 other countries (Figure ​(Figure1D).1D). To illustrate the HDX MS applications in much greater detail, we have divided the remainder of the article into six sections that each discuss one of the topical classifications shown in Figure ​Figure11E.