Biology Reference
In-Depth Information
is an automated script for generating a CG representation of a protein from an atom-
istic structure (i.e., a PDB structure). The generated CGmodel can be then embedded
into a membrane bilayer following similar methods as the one explained earlier. Al-
ternatively, certain molecular engines such as GROMACS have already created spe-
cific tools for this purpose, namely, the “g_membed” command, incorporated within
the last version of this software. Similarly to all-atom simulations, once the GPCR
monomer is embedded in the membrane, the system is solvated and ionized. How-
ever, at this point, the unit cell created is multiplied with a view to create a larger
system (
Fig. 4.4
) containing as many GPCRs as allowed by the computational re-
sources available. For example, in their recent study
Periole et al. (2012)
were able
to simulate ten independent systems containing 16 rhodopsin monomers each and, in
addition, they created a larger system containing 64 rhodopsin monomers. While all
10 systems were simulated up to 10
m
s* (please note an asterisk is used to indicate an
effective time that accounts for the speedup factor of four typically used MARTINI
CG simulations;
Ramadurai et al., 2010
), they simulated the large system up to
100
m
s*, confirming the valuable performance of CG simulations when dealing with
large systems.
All in all, CG simulations remain the preferred simulation technique for
gener
ating long trajectories of systems that are otherwise outsized for all-atom sim-
ulations, as in the case of GPCR oligomerization studies. Nevertheless, the combi-
nation of both CG and all-atom simulations can enrich this approach even further. In
this line, various studies describe the use of biased and nonbiased CG and all-atom
MD to assess to study the dimerization interface of certain GPCRs such as the
d
-opi-
oid receptor (
Johnston et al., 2011; Provasi et al., 2010
). The aim of these studies is to
either structurally describe the most energetically favorable interface (
Johnston
et al., 2011
) or assess the stability of such interface in an attempt to characterize
the association lifetime of GPCR dimers (
Provasi et al., 2010
). Yet, studying the role
that membrane lipids have on GPCR dimerization should be the one of the focuses of
attention, not only because other studies are pointing towards their potential involve-
ment, as we discuss herein, but also because, today, we do have some tools available
for this aim such as CG simulations.
References
Bartels, T., Lankalapalli, R. S., Bittman, R., Beyer, K., & Brown, M. F. (2008). Raftlike mix-
tures of sphingomyelin and cholesterol investigated by solid-state 2H NMR spectroscopy.
