Interpreting hydrogen-deuterium exchange experiments with molecular simulations: Tutorials and applications of the HDXer ensemble reweighting software

This article presents a collection of tutorials, and accompanying guidance, for the HDXer ensemble reweighting software package. The tutorial files themselves are available within the main HDXer software package.

The HDXer software has two main functions:

1. To predict H-D exchange rates from a candidate ensemble of protein structures, for example from molecular simulations
2. To objectively reweight the conformational populations present in a candidate ensemble to conform to experimental hydrogen-deuterium exchange data

Here, we first describe the HDXer approach, theory, and implementation. We then guide users through tutorials demonstrating practical applications of experimental data preparation, predicting HDX levels from molecular simulations, and performing ensemble reweighting analyses. Finally, we provide a practical discussion of the capabilities and limitations of the HDXer methods, including recommendations for a user's own analyses.

List of Authors

• P.S. Lee, NINDS, National Institutes of Health, Bethesda, MD, USA
• R.T. Bradshaw, NINDS, National Institutes of Health, Bethesda, MD, USA
• F. Marinelli, NHLBI, National Institutes of Health, Bethesda, MD, USA
• K. Kihn, University of Maryland, Baltimore, MD, USA
• A. Smith, University of Maryland, Baltimore, MD, USA
• P.L. Wintrode, University of Maryland, Baltimore, MD, USA
• D.J. Deredge, University of Maryland, Baltimore, MD, USA
• J.D. Faraldo-Gómez, NHLBI, National Institutes of Health, Bethesda, MD, USA
• L.R. Forrest, NINDS, National Institutes of Health, Bethesda, MD, USA

Paper writing as code development

This paper is being developed as a living document, open to changes from the community. You can read more about the concept of writing a paper in the same way one would write software code in the essay "Paper writing as code development". If you have comments or suggestions, we welcome them! Please submit them as issues to this GitHub repository so they can be recorded and given credit for the contribution. Specific changes can be proposed via pull requests.

List of Released Versions

• v0.1: Submitted to LiveCoMS
• v0.2: Resubmission post-review
• v1.0: First published version (currently ASAP version)

Changelog

• 29 June 2021: Initial commit of document prior to submission
• 03 Dec 2021: Resubmission of v0.2 after changes post-review
• 26 Jan 2022: Upload & publication of ASAP version 1.0
• 24 Aug 2022: Upload & publication of final version 1.0