title: Molecular simulation-based structural prediction of protein complexes in mass spectrometry: the human insulin dimer.
abstract: Protein electrospray ionization (ESI) mass spectrometry (MS)-based techniques are widely used to provide insight into structural proteomics under the assumption that non-covalent protein complexes being transferred into the gas phase preserve basically the same intermolecular interactions as in solution. Here we investigate the applicability of this assumption by extending our previous structural prediction protocol for single proteins in ESI-MS to protein complexes. We apply our protocol to the human insulin dimer (hIns2) as a test case. Our calculations reproduce the main charge and the collision cross section (CCS) measured in ESI-MS experiments. Molecular dynamics simulations for 0.075 ms show that the complex maximizes intermolecular non-bonded interactions relative to the structure in water, without affecting the cross section. The overall gas-phase structure of hIns2 does exhibit differences with the one in aqueous solution, not inferable from a comparison with calculated CCS. Hence, care should be exerted when interpreting ESI-MS proteomics data based solely on NMR and/or X-ray structural information.
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences (joint venture of RWTH Aachen University and Forschungszentrum Jülich, Germany), Jülich, Germany and Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, Jülich, Germany; Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Li
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences (joint venture of RWTH Aachen University and Forschungszentrum Jülich, Germany), Jülich, Germany and Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, Jülich, Germany; Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Giulia
authors.initials: G
authors.lastname: Rossetti
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences (joint venture of RWTH Aachen University and Forschungszentrum Jülich, Germany), Jülich, Germany and Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dreyer
authors.affiliation: Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Simone
authors.initials: S
authors.lastname: Raugei
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences (joint venture of RWTH Aachen University and Forschungszentrum Jülich, Germany), Jülich, Germany and Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Ippoliti
authors.affiliation: Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences (joint venture of RWTH Aachen University and Forschungszentrum Jülich, Germany), Jülich, Germany and Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D006801:Humans; D007328:Insulin / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D040901:Proteomics / Q000379:methods*; D013816:Thermodynamics
chemical_list: D007328:Insulin; C034329:insulin dimers