title: Multiple Binding Poses in the Hydrophobic Cavity of Bee Odorant Binding Protein AmelOBP14.
abstract: In the first step of olfaction, odorants are bound and solubilized by small globular odorant binding proteins (OBPs) which shuttle them to the membrane of a sensory neuron. Low ligand affinity and selectivity at this step enable the recognition of a wide range of chemicals. Honey bee Apis mellifera's OBP14 (AmelOBP14) binds different plant odorants in a largely hydrophobic cavity. In long molecular dynamics simulations in the presence and absence of ligand eugenol, we observe a highly dynamic C-terminal region which forms one side of the ligand-binding cavity, and the ligand drifts away from its crystallized orientation. Hamiltonian replica exchange simulations, allowing exchanges of conformations sampled by the real ligand with those sampled by a noninteracting dummy molecule and several intermediates, suggest an alternative, quite different ligand pose which is adopted immediately and which is stable in long simulations. Thermodynamic integration yields binding free energies which are in reasonable agreement with experimental data.
authors.affiliation: Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences , Muthgasse 18, 1190 Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Pechlaner
authors.affiliation: Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences , Muthgasse 18, 1190 Vienna, Austria.
authors.forename: Chris
authors.initials: C
authors.lastname: Oostenbrink
mesh_terms: D000818:Animals; D001516:Bees; D018360:Crystallography, X-Ray; D005054:Eugenol / Q000737:chemistry / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D019476:Insect Proteins / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055550:Protein Stability; D018035:Receptors, Odorant / Q000737:chemistry* / Q000187:drug effects; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D019476:Insect Proteins; D008024:Ligands; D018035:Receptors, Odorant; C045648:odorant-binding protein; D014867:Water; D005054:Eugenol