Characteristics of a Folate Receptor‑α Anchored into a Multilipid Bilayer Obtained from Atomistic Molecular Dynamics Simulations

Thorough computational description of the properties
of membrane-anchored
protein receptors, which are important for example in the context
of active targeting drug delivery, may be achieved by models representing
as close as possible the immediate environment of these macromolecules.
An all-atom bilayer, including 35 different lipid types asymmetrically
distributed among the two monolayers, is suggested as a model neoplastic
cell membrane. One molecule of folate receptor-α (FRα)
is anchored into its outer leaflet, and the behavior of the system
is explored by atomistic molecular dynamics simulations. The total
number of atoms in the model is ∼185 000. Three 1-μs-long
simulations are carried out, where physiological conditions (310 K
and 1 bar) are maintained with three different pressure scaling schemes.
To evaluate the structure and the phase state of the membrane, the
density profiles of the system, the average area per lipid, and the
deuterium order parameter of the lipid tails are calculated. The bilayer
is in liquid ordered state, and the specific arrangement varies between
the three trajectories. The changes in the structure of FRα
are investigated and are found time- and ensemble-dependent. The volume
of the ligand binding pocket fluctuates with time, but this variation
remains independent of the more global structural alterations. The
latter are mostly “waving” motions of the protein, which
periodically approaches and retreats from the membrane. The semi-isotropic
pressure scaling perturbs the receptor most significantly, while the
isotropic algorithm induces rather slow changes. Maintaining constant
nonzero surface tension leads to behavior closest to the experimentally
observed one.