Molecular Simulation-Based Structural Prediction of Protein Complexes in Mass Spectrometry:The Human Insulin Dimer
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(hlns2)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 hlns2 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.
Jinyu Li Giulia Rossetti Jens Dreyer Simone Raugei Emiliano Ippoliti Bernhard Lüscher Paolo Carloni
Computational Biophysics,German Research School for Simulation Sciences(joint venture of RWTH Aachen Computational Biophysics,German Research School for Simulation Sciences(joint venture of RWTH Aachen Computational Biophysics,German Research School for Simulation Sciences(joint venture of RWTH Aachen Fundamental and Computational Sciences Directorate,Pacific Northwest National Laboratory,Richland,Wa Institute of Biochemistry and Molecular Biology RWTH Aachen University,Aachen,Germany
国内会议
大连
英文
594-603
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）