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@ARTICLE{Pirona:1024691,
      author       = {Pirona, Lorenza and Ballabio, Federico and Alfonso-Prieto,
                      Mercedes and Capelli, Riccardo},
      title        = {{C}alcium-driven {I}n {S}ilico {I}nactivation of a {H}uman
                      {O}lfactory {R}eceptor},
      journal      = {bioRxiv beta},
      address      = {Cold Spring Harbor},
      publisher    = {Cold Spring Harbor Laboratory, NY},
      reportid     = {FZJ-2024-02364},
      year         = {2024},
      note         = {Preprint publicly available; peer-reviewed version was
                      published in Journal of Chemical Information and Modeling
                      (doi: 10.1021/acs.jcim.4c00249)},
      abstract     = {Conformational changes as well as molecular determinants
                      related to the activation and inactivation of olfactory
                      receptors are still poorly understood due to the intrinsic
                      difficulties in the structural determination of this GPCR
                      family. Here, we perform, for the first time, the in silico
                      inactivation of the human olfactory receptor OR51E2,
                      highlighting the possible role of calcium in this receptor
                      state transition. Using molecular dynamics simulations, we
                      show that a divalent ion in the ion binding site,
                      coordinated by two acidic residues at positions 2.50 and
                      3.39 conserved across most ORs, stabilizes the receptor in
                      its inactive state. In contrast, protonation of the same two
                      acidic residues is not sufficient to drive inactivation
                      within the µs timescale of our simulations. Our findings
                      suggest a novel molecular mechanism for OR inactivation,
                      potentially guiding experimental validation and offering
                      insights into the possible broader role of divalent ions in
                      GPCR signaling.},
      cin          = {IAS-5 / INM-9},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
      pnm          = {5241 - Molecular Information Processing in Cellular Systems
                      (POF4-524) / DFG project 291198853 - FOR 2518: Funktionale
                      Dynamik von Ionenkanälen und Transportern - DynIon -
                      (291198853) / DFG project 329460521 - Protonentransfer und
                      Substraterkennung in SLC17-Transportern (329460521)},
      pid          = {G:(DE-HGF)POF4-5241 / G:(GEPRIS)291198853 /
                      G:(GEPRIS)329460521},
      typ          = {PUB:(DE-HGF)25},
      doi          = {10.1101/2024.01.31.578070},
      url          = {https://juser.fz-juelich.de/record/1024691},
}