title: Toward molecular mechanism of xenon anesthesia: a link to studies of xenon complexes with small aromatic molecules.
abstract: The present study illustrates the steps toward understanding molecular mechanism of xenon anesthesia by focusing on a link to the structures and spectra of intermolecular complexes of xenon with small aromatic molecules. A primary cause of xenon anesthesia is attributed to inhibition of N-methyl-D-aspartate (NMDA) receptors by an unknown mechanism. Following the results of quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) calculations we report plausible xenon action sites in the ligand binding domain of the NMDA receptor, which are due to interaction of xenon atoms with aromatic amino-acid residues. We rely in these calculations on computational protocols adjusted in combined experimental and theoretical studies of intermolecular complexes of xenon with phenol. Successful reproduction of vibrational shifts in molecular species upon complexation with xenon measured in low-temperature matrices allowed us to select a proper functional form in density functional theory (DFT) approach for use in QM subsystems, as well as to calibrate force field parameters for MD simulations. The results of molecular modeling show that xenon atoms can compete with agonists for a place in the corresponding protein cavity, thus indicating their active role in anesthetic action.
authors.affiliation: †Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russian Federation.
authors.forename: Natalya N
authors.initials: NN
authors.lastname: Andrijchenko
authors.affiliation: †Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russian Federation.
authors.forename: Alexander Yu
authors.initials: AY
authors.lastname: Ermilov
authors.affiliation: ‡Department of Chemistry, University of Helsinki, P.O. Box 55, Helsinki FI-00014, Finland.
authors.forename: Leonid
authors.initials: L
authors.lastname: Khriachtchev
authors.affiliation: ‡Department of Chemistry, University of Helsinki, P.O. Box 55, Helsinki FI-00014, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Räsänen
authors.affiliation: †Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russian Federation.|§N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina 4, Moscow 119334, Russian Federation.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Nemukhin
mesh_terms: D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016202:N-Methylaspartate / Q000737:chemistry; D011789:Quantum Theory; D014978:Xenon / Q000737:chemistry*
chemical_list: D006841:Hydrocarbons, Aromatic; D014978:Xenon; D016202:N-Methylaspartate