How useful is ion mobility mass spectrometry for structural biology? The relationship between protein crystal structures and their collision cross sections in the gas phase Ewa Jurneczko and Perdita E. Barran * Received 3rd June 2010, Accepted 4th August 2010 DOI: 10.1039/c0an00373e The technique of ion mobility mass spectrometry (IM-MS) has become of increasing interest for rapid analysis of the conformations adopted by biological macromolecules. It is currently used routinely for analysis of explosives and illegal substances in airport and military security. In biophysical research, it can be used to determine the temperature dependent rotationally averaged collision cross section of gas-phase ions of proteins and nucleic acids along with their mass to charge ratios. Nanoelectrospray ionisation allows the gentle transfer of intact biomolecules from solutions in which the native form(s) are present, into the solvent free environment of a mass spectrometer. It is believed by many researchers that the experimental collision cross sections of these molecules should have some relationship to crystal structure coordinates. In this review we outline the different experimental methods that can be used to measure ion mobility; we also describe methods used to calculate collision cross sections from input coordinates. Following this survey of the methodological approaches to IM-MS, we then summarise IM-MS data published to date for some monomeric peptides and small soluble proteins, along with collision cross sections calculated from their crystal structure coordinates. Finally we consider the relationship between experimental gas-phase conformations and those adopted in crystals and give an outlook on the application of IM-MS as a tool for structural biology. The School of Chemistry, The University of Edinburgh, Edinburgh, UK. E-mail: perdita.barran@ed.ac.uk; Tel: +44 (0)131 650 7533 Ewa Jurneczko Ewa Jurneczko is a post- graduate student in the School of Chemistry at Edinburgh University where she is under- taking a PhD in biological mass spectrometry sponsored by the BBSRC and Waters. Her current research in the Barran group investigates the effects of different drift gases on protein ions using IM-MS, as well as exploring the use of IM-MS to examine intrinsic disorder in proteins. She received her BSc in Forensic Science from the University of Northumbria in 2009, which involved a year in industry working for Aptuit. Perdita E: Barran Perdita Barran is currently a Senior Lecturer in Biophysical Chemistry at the University of Edinburgh. She graduated from Manchester University with a degree in Chemistry with Industrial Experience (1994), and from Sussex University with a PhD in Chemical Physics (1998) under the supervision of Professors Tony Stace and Sir Harry Kroto. She worked as a post-doctoral researcher for Tony Stace, before moving to the University of California Santa Barbara to work with Mike Bowers. She was awarded an EPSRC Advanced Research Fellowship in 2002 which allowed her to commence independent research at Edinburgh University in 2003. 20 | Analyst, 2011, 136, 20–28 This journal is ª The Royal Society of Chemistry 2011 Dynamic Article Links C < Analyst Cite this: Analyst, 2011, 136, 20 www.rsc.org/analyst CRITICAL REVIEW Downloaded on 24 March 2013 Published on 31 August 2010 on http://pubs.rsc.org | doi:10.1039/C0AN00373E View Article Online / Journal Homepage / Table of Contents for this issue