Mesoscopic models of lipid bilayers and bilayers with embedded ...

98 Mesoscopic model for lipid bilayers with embedded proteins
they do not take into full account the three dimensional structure of the bilayer), and,
for example, they can not be used to investigate the lipid-induced protein tilting.
Simulations on more realistic models, such as all-atom models for lipid bilayers with
embedded proteins, have anyway confirmed that, at least within a time of the order
of the nanoseconds, a mismatched protein may induce a deformation of the lipid bilayer
structure [10, 63, 170], and that the deformation is of the exponential type [11].
The same type of studies have also shown that—although to reduce a possible hydrophobic
mismatch synthetic peptides may prefer to deform the lipid bilayer, rather
than undergo tilting [171]—tilting may also occur for membrane peptides [7,8]. Incidentally,
the results from these studies indicated that the helical-peptides experience
a slight bend in the middle of the helix.
No matter the huge body of experimental and theoretical studies on lipid bilayers
with embedded proteins, issues such as the range of the protein-induced lipid bilayer
perturbation, its dependence on protein size, and the occurrence of protein tilting (or
even bending) to adjust for hydrophobic mismatch, are still a matter of debate. Here
we want to focus on these issues by adopting the DPD simulation method to study
the behavior of a mesoscopic model for lipid bilayers with embedded proteins. We
have focused our attention on the perturbation caused by a membrane protein on
the surrounding lipids, its possible dependence on hydrophobic mismatch, protein
size, and on temperature. We have investigated whether and to which extent—due to
hydrophobic mismatch and via the cooperative nature of the system—a protein may
prefer to tilt (with respect to the normal to the bilayer plane), rather than to induce a
bilayer deformation without (or even with) tilting.
7.2 Computational details
7.2.1 Lipid and protein models
Within the mesoscopic approach, each molecule of the system (or groups of molecules)
is coarse-grained by a set of beads. In particular, to model the bilayer and the
embedded proteins, we consider three types of beads: a water-like bead, labeled ’w’;
a hydrophilic bead, labeled ’h’, which models a part of the headgroup of either the
lipid or the protein; and a hydrophobic bead, labeled either ’tL’ or ’tP’, depending on
whether it refers to a portion of the lipid hydrocarbon chain or a portion of the hydrophobic
region of protein, respectively. The systems that we have simulated are
made of model lipids having three headgroup beads and two tails of five beads each;
this corresponds to the case of acyl chains with fourteen carbon atoms, namely to a
model for a dimyristoylphosphatidylcholine (DMPC) phospholipid, as illustrated in
figure 2.2 of Chapter 2, and in figure 7.1(a). Within the model formulation, a protein
is considered as a rod-like object, with no appreciable internal flexibility, and characterized
by a hydrophobic length dP. The model for the transmembrane protein is