Supplemental Material for:
On the Application of the MARTINI Coarse-Grained Model to Immersion of
a Protein in a Phospholipid Bilayer
Ghulam Mustafa1#), Prajwal P. Nandekar 1#), Xiaofeng Yu1) and Rebecca C Wade1,2,3)
1) Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloß-Wolfsbrunnenweg
35, 69118 Heidelberg, Germany
2) Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, INF 282, 69120 Heidelberg,
Germany
3) Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, INF 368, 69120 Heidelberg, Germany
#
Authors with equal contribution.
*Corresponding Authors: Ghulam Mustafa, Rebecca Wade Email: Rebecca.wade@h-its.org
The Supplemental Material consists of 1 Table and 5 Figures.
TABLE SI. Mean and standard deviation for angles and distances defining the CYP globular domain
position with respect to the bilayer computed from averaging over snapshots obtained after
convergence of the trajectories for the CYP-bilayer systems. For CYP3A4, the coarse-grain (CG)
simulations using the PW and NPW models and different non-bonded interaction treatments show
similar angles and distances and these are similar to those in AA simulations, showing convergence of
the protein orientation and depth in the bilayer. In CG simulations for the other CYPs, different
converged orientations and depths are obtained, showing that these are dependent on the protein
sequence and structure.
Protein
Method
Water
model
CYP3A4
CG
NPW
Nonbonded
treatment
RF
139.3±6.1
TM helix
tilt angle γ
(°)
30.5±7.4
COM
distance
(Å)
42.0±1.9
CYP3A4
CG
PW
66.2±4.6
144.3±5.0
34.4±8.3
42.1±1.4
CYP3A4
CG
15
64.6±6.4
139.7±6.4
29.5±9.2
44.2±2.2
CYP3A4
PME
1
58.1±2.2
134.9±2.7
39.3±4.2
43.9±1.6
NPW
RF
15
84.5±9.2
118.8±8.9
16.0±6.7
45.4±1.8
CG
NPW
RF
15
99.2±6.6
135.9±6.5
18.0±6.0
45.1±1.9
CYP2C9
CG
NPW
RF
15
88.4±6.7
111.8±6.8
15.5±7.0
42.3±2.0
CYP2C19
CG
NPW
RF
15
96.9±7.1
130.7±14.1
13.0±6.7
47.3±1.9
Epsr
Angle α
(°)
Angle β (°)
15
64.7±6.5
PME
2.5
PW
Shift
AA
TIP3P
CYP1A1
CG
CYP1A2
FIG S1. The distribution of lipid molecules into boundary and non-boundary lipids represented by
green and blue polygons for the representative structure in all-atom representation obtained at the end
of the CG simulation with the NPW model and RF. The red * mark shows the center of mass of each
lipid molecule. The area per lipid is computed by Voronoi tessellation for non-boundary and Monte
Carlo integration for boundary lipids using the VTMC method.1
FIG. S2. The geometric parameters observed for CYP3A4 in the membrane in the all-atom MD
simulation. These show a stable orientation of the globular domain of the protein during the simulation.
a
b
FIG S3. Comparison between the orientation and depth of the globular domain of CYP3A4 in the
bilayer in the CG and AA simulations. Normalized distributions of the distance between the CoM of
the globular domain of the protein and the CoM of the lipid bilayer are shown for CG in black and AA
in red (a); and the angle α is shown in black for CG and red for AA and the angle β is shown in green
for CG and in blue for AA (b).
a
b
c
)
d
FIG. S4. Convergence of the position of different CYPs (a.1A1, b.1A2, c.2C9 and d.2C19) with respect
to the bilayer in CG simulations with the NPW model and with RF run with GROMACS 5.0.4. The
distance between the center of mass (CoM) of the globular domain of the protein and the CoM of the
bilayer is shown by the green line, the angle αbetween v1 and the z-axis by the black line, and the angle
β between v2 and the z-axis by the red line.
a
b
FIG. S5 a,b. The representative frame (yellow cartoon) from the CG simulation of CYP3A4 with the
NPW model is superimposed on the coordinates obtained from the OPM database (a) PDB id: 1TNQ
(cyan), (b) PDB id: 3NXU (green). The phosphate atoms in the head groups of the simulated bilayer
are shown as orange spheres and the surface of the membrane provided by the OPM database is shown
by the disks of pink and blue dummy atoms. Although the CG simulations were performed using the
1TNQ structure, the orientation in the membrane obtained agrees better with the orientation for the
3NXU structure in the OPM database.
REFERENCES:
1
T. Mori, F. Ogushi, and Y. Sugita, J. Comput. Chem. 33, 286 (2012).