Weighing-up protein dynamics: the combination of native mass spectrometry and molecular dynamics simulations

• Published in: Current opinion in structural biology 2019-02, Vol.54, p.50-58
• Main Authors: Marklund, Erik G, Benesch, Justin LP
• Format: Article
• Language: English
• Subjects: Cell Membrane - metabolism; Mass Spectrometry; Molecular Dynamics Simulation; Proteins - chemistry; Proteins - metabolism; Small Molecule Libraries - metabolism
• ISSN: 0959-440X; 1879-033X; 1879-033X
• DOI: 10.1016/j.sbi.2018.12.011

•Native mass spectrometry provides coarse structural and dynamics information.•Molecular dynamics simulations operate at the atomic level.•Integrating these approaches addresses the individual weaknesses of each.•The combination has great potential for structural and dynamical proteomics. Structural dynamics underpin biological function at the molecular level, yet many biophysical and structural biology approaches give only a static or averaged view of proteins. Native mass spectrometry yields spectra of the many states and interactions in the structural ensemble, but its spatial resolution is limited. Conversely, molecular dynamics simulations are innately high-resolution, but have a limited capacity for exploring all structural possibilities. The two techniques hence differ fundamentally in the information they provide, returning data that reflect different length scales and time scales, making them natural bedfellows. Here we discuss how the combination of native mass spectrometry with molecular dynamics simulations is enabling unprecedented insights into a range of biological questions by interrogating the motions of proteins, their assemblies, and interactions.