Atomistic-level investigation
of olfactory receptors (ORs) is a
challenging task due to the experimental/computational difficulties
in the structural determination/prediction for members of this family
of G-protein coupled receptors. Here, we have developed a protocol
that performs a series of molecular dynamics simulations from a set
of structures predictedde novoby recent machine
learning algorithms and apply it to a well-studied receptor, the human
OR51E2. Our study demonstrates the need for simulations to refine
and validate such models. Furthermore, we demonstrate the need for
the sodium ion at a binding site near D2.50and E3.39to stabilize the inactive state of the receptor. Considering the
conservation of these two acidic residues across human ORs, we surmise
this requirement also applies to the other ∼400 members of
this family. Given the almost concurrent publication of a CryoEM structure
of the same receptor in the active state, we propose this protocol
as anin silicocomplement to the growing field of
ORs structure determination.