Biology Reference
In-Depth Information
FIGURE 4.3
Membrane-deformation profile u(x,y) of the simulation of a serotonin 5-HT
2A
receptor
embedded in a pure C
18:0
-C
22:6
PC bilayer. The figure depicts a membrane-deformation
profile calculated out of the last 200 ns of this trajectory. Beads represent the averaged
membrane leaflets based on the positions of lipid P atoms. A color gradient scale illustrates for
this particular simulation the minimum (deep blue) and maximum (deep red) values of
membrane deformation, u(x,y), being 3.85 and
0.62
˚
, respectively. Interestingly, the
membrane-to-protein adaptation is higher for the intracellular leaflet when compared to the
extracellular one. It is important to note that the formulation of the membrane-deformation
variable u(x,y) herein calculated does not account for local adaptations of each leaflet
but for the overall adaptation of the bilayer.
C
16:0
-C
18:1
PC/cholesterol) (
Fig. 4.3
). Interestingly, these predictions are in good agree-
ment with experimental results (
Palczewski et al., 2000
) and other recent CGMD sim-
ulations of this protein (
Periole, Huber, Marrink, & Sakmar, 2007
).
Recently, the same group (Mondal et al.) has studied the effect of ligands
with different pharmacological properties on the remodeling of membrane in
GPCR-membrane simulations (
Mondal et al., 2011; Shan, Khelashvili, Mondal,
Mehler, & Weinstein, 2012
). In these studies, they analyzed a set of MD trajectories
they had previously published (
Shan, Khelashvili, Mondal, & Weinstein, 2011
).
Therein, they performed MD simulations of the serotonin (5-hydroxytryptamine,
5-HT) 5-HT
2A
receptor in complex with either the full agonist 5-HT, the partial ag-
onist lysergic acid diethylamide (LSD), or the inverse agonist ketanserin (KET) and
inserted into a multicomponent membrane (7:7:6 C
18:0
-C
22:6
PC/C
16:0
-C
18:1
PC/cho-
lesterol). The MD trajectories showed conformational changes in response to the dif-
ferent ligand binding at TM1, TM4, and TM6 helices. The 3D-CTMD analysis of
those trajectories revealed different patterns of bilayer deformations around the
