Exploring membrane and protein dynamics with dissipative particle dynamics.

In this chapter, we review recent approaches and results when studying membrane and protein dynamics by means of dissipative particle dynamics (DPD). First, we introduce and discuss DPD as a method, for example, the choice of the thermostat, which is of interest when constructing a DPD code. Then, we review important results on pure membranes and lipid-water systems that have been obtained with DPD. Finally, we focus on simulations of membranes with associated or embedded model proteins that may trigger future research on the fundamental interactions of lipids and proteins in the context of living cells.

Dynamic structure formation of peripheral membrane proteins.

Using coarse-grained membrane simulations we show here that peripheral membrane proteins can form a multitude of higher-order structures due to membrane-mediated interactions. Peripheral membrane proteins characteristically perturb the lipid bilayer in their vicinity which supports the formation of protein assemblies not only within the same but surprisingly also across opposing leaflets of a bilayer. In addition, we also observed the formation of lipid-protein domains on heteregeneous membranes. The clustering ability of proteins, as quantified via the potential of mean force, is enhanced when radius and hydrophobic penetration depth of the proteins increases. Based on our data, we propose that membrane-mediated cluster formation of peripheral proteins supports protein assembly in vivo and hence may play a pivotal role in the formation of templates for signaling cascades and in the emergence of transport intermediates in the secretory pathway.

On the role of acylation of transmembrane proteins.

Acylation is a frequent means to ensure membrane association of a variety of soluble proteins in living cells. However, many transmembrane proteins are palmitoylated, indicating that this posttranslational modification may also serve as a means to regulate protein trafficking. Based on coarse-grained membrane simulations, we find that protein acylation significantly alters the tilting of transmembrane proteins with respect to the bilayer normal. In addition, the proteins' partitioning behavior and cluster formation ability due to hydrophobic mismatching is strongly altered. Based on our results, we propose that acylation is a potent means to regulate the trafficking of transmembrane proteins along the early secretory pathway.