Transmembrane proteins interact which each other directly or mediated via their influence on the lipid membrane structure and fluctuations. The interactions govern the dynamics of integral protein insertion, (re-) folding and assembly in functional oligomeric structures such as the tetrameric potassium channel KcsA.
On the other hand, antimicrobial peptides as defensins and magainins aggregate supposedly either in the lipid head group region or in a transmembrane fashion leading to permeation and rupture of bacterial membranes. The mechanisms of these processes are very difficult to study experimentally.
The objective of our research proposal is to model protein-membrane interactions by multi-scale molecular dynamics simulation. Using a quantitative coarse g rain description, we can access the spatial and temporal scales of these processes, which are too large for direct simulation with atomistic molecular dynamics.
However, using a special interface between our coarse grain representation and the all atom rep resentation of the system, we can connect the mesoscale phenomena to the underlying atomistic details.
Using special techniques as path sampling and the novel metadynamics method, we will map out the free energy landscape of interacting transmembrane prote ins in terms of generic hydrophobic, hydrophilic and electrostatic interactions, specific protein residue interactions, and interactions induced by lipid ordering and friction.
If successful, the results are expected to gain insight in how peptides and proteins insert and interact in biomembranes which is of interest to a wide variety of applications, in particular for drug design and for the development of biomimetic antimicrobials.
Fields of science
Call for proposal
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