title: Proton Dynamics in Protein Mass Spectrometry.
abstract: Native electrospray ionization/ion mobility-mass spectrometry (ESI/IM-MS) allows an accurate determination of low-resolution structural features of proteins. Yet, the presence of proton dynamics, observed already by us for DNA in the gas phase, and its impact on protein structural determinants, have not been investigated so far. Here, we address this issue by a multistep simulation strategy on a pharmacologically relevant peptide, the N-terminal residues of amyloid-β peptide (Aβ(1-16)). Our calculations reproduce the experimental maximum charge state from ESI-MS and are also in fair agreement with collision cross section (CCS) data measured here by ESI/IM-MS. Although the main structural features are preserved, subtle conformational changes do take place in the first ∼0.1 ms of dynamics. In addition, intramolecular proton dynamics processes occur on the picosecond-time scale in the gas phase as emerging from quantum mechanics/molecular mechanics (QM/MM) simulations at the B3LYP level of theory. We conclude that proton transfer phenomena do occur frequently during fly time in ESI-MS experiments (typically on the millisecond time scale). However, the structural changes associated with the process do not significantly affect the structural determinants.
authors.affiliation: College of Chemistry, Fuzhou University , 350002 Fuzhou, China.
authors.forename: Jinyu
authors.identifier: http://orcid.org/0000-0002-8220-049X
authors.initials: J
authors.lastname: Li
authors.affiliation: Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich , 52425 Jülich, Germany.|Faculty of Mathematics, Computer Science and Natural Sciences, RWTH-Aachen University , 52056 Aachen, Germany.|Computation-Based Science and Technology Research Center, Cyprus Institute , 2121 Aglantzia, Nicosia, Cyprus.
authors.forename: Wenping
authors.identifier: http://orcid.org/0000-0001-9176-5444
authors.initials: W
authors.lastname: Lyu
authors.affiliation: Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich , 52425 Jülich, Germany.|Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University , 52062 Aachen, Germany.|Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich , D-52425 Jülich, Germany.
authors.forename: Giulia
authors.initials: G
authors.lastname: Rossetti
authors.affiliation: Biomolecular & Analytical Mass Spectrometry group, Department of Chemistry, University of Antwerp , 2000 Antwerpen, Belgium.
authors.forename: Albert
authors.initials: A
authors.lastname: Konijnenberg
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca , Piazza della Scienza 2, 20126 Milan, Italy.
authors.forename: Antonino
authors.identifier: http://orcid.org/0000-0002-1489-272X
authors.initials: A
authors.lastname: Natalello
authors.affiliation: Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich , 52425 Jülich, Germany.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Ippoliti
authors.affiliation: Joint BSC-IRB Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, Barcelona 08028, Spain.|Departament de Bioquímica i Biomedicina, Facultat de Biologia, Universitat de Barcelona , Avgda Diagonal 647, Barcelona 08028, Spain.
authors.forename: Modesto
authors.identifier: http://orcid.org/0000-0002-8608-3278
authors.initials: M
authors.lastname: Orozco
authors.affiliation: Biomolecular & Analytical Mass Spectrometry group, Department of Chemistry, University of Antwerp , 2000 Antwerpen, Belgium.|Astbury Centre for Structural Molecular Biology, University of Leeds , Leeds LS2 9JT, United Kingdom.|School of Molecular and Cellular Biology, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca , Piazza della Scienza 2, 20126 Milan, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Grandori
authors.affiliation: Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich , 52425 Jülich, Germany.|JARA-HPC, 52425 Jülich, Germany.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D056004:Molecular Dynamics Simulation; D010455:Peptides; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011522:Protons; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D010455:Peptides; D011506:Proteins; D011522:Protons