Conformational evolution of ubiquitin ions in electrospray mass spectrometry: Molecular dynamics simulations at gradually increasing temperatures

Elad Segev*, Thomas Wyttenbach, Michael T. Bowers, R. Benny Gerber

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Evidence from cross section data indicates that ubiquitin +13 ions lose their secondary and tertiary structure in mass spectrometric experiments. These transitions from the folded state into the near linear final structure occur at the experimental temperatures on time scales that are far too long for conventional molecular dynamics simulations. In this study, an approach to mass spectrometric unfolding processes is developed and a detailed application to an ubiquitin +13 ion system is presented. The approach involves a sequence of molecular dynamics simulations at gradually increasing temperatures leading to identification of major intermediate states, and the unfolding pathway. The unfolding rate at any temperature can then be calculated by a Rice-Ramsperger-Kassel (RRK) approach. For ubiquitin +13, three interesting intermediate states were found and the final near linear geometry was computed. The several relevant energy barriers calculated for the process are in the range of 7 to 15 kcal mol-1. The unfolding time scale at 300 K was computed to be 2 ms. Cross section calculations using a hard sphere scattering model were carried out for the final structure and found to be in good accord with the results of electrospray experiments supporting the theoretical model used. The approach employed here should be applicable to any other solvent-free protein system.

Original languageEnglish
Pages (from-to)3077-3082
Number of pages6
JournalPhysical Chemistry Chemical Physics
Volume10
Issue number21
DOIs
StatePublished - 2008

Fingerprint

Dive into the research topics of 'Conformational evolution of ubiquitin ions in electrospray mass spectrometry: Molecular dynamics simulations at gradually increasing temperatures'. Together they form a unique fingerprint.

Cite this