Journal
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Volume 55, Issue 12, Pages 2633-2643Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jcim.5b00673
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Funding
- Vienna Science and Technology Fund (WWTF) [LS08-QM03]
- European Research Council (ERC) [260408]
- European Research Council (ERC) [260408] Funding Source: European Research Council (ERC)
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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.
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