Multiple Binding Poses in the Hydrophobic Cavity of Bee Odorant Binding Protein AmelOBP14

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.