One subject of interest in our group concerns the modeling of the structure and the interaction of biological membranes immersed in water. In particular, we are interested in the interactions between membranes at nanometer separations where the presence of the hydration water becomes important. One technical problem which we solved (E. Schneck et al. PNAS 109, 14405-9 (2012)) is to keep the chemical potential of the water molecules constant for different membrane separations. By using Molecular Dynamics we investigate the influence of the lipid head group structure, the fluidity of the membranes, dissolved ions, membrane shearing, etc. In the case when the membranes exhibit hydrophobic character, the water slab between the membranes at small separations becomes unstable and decomposes into droplets and menisci that bridge both surfaces (as shown in the figure).
Multivalency is an important design principle in nature. It plays a key-role in a wide range of chemical, biological and medical systems, such as hormone binding or virus-cell interactions. The basic principle of multivalency is the simultaneous binding of several relatively weak binding partners, in order to strengthen the over-all interaction. For the development of new drugs targeting multivalent receptors it crucial to optimize the design of suitable ligands. In our project we use a multiscale approach to describe multivalent interactions theoretically. Based on the investigation of individual ligand-receptor binding sides on the atomistic level, by molecular dynamic simulations, a gorse grained model is developed that allows to determine the binding constant of multivalent ligands. Our aim is to derive general rules for the optimal design of multivalent ligands (J. Vonnemann et al. JACS 137, 2572 (2015)).
Furthermore, we examine virus-inhibition-assays, for example for the influenca virus. We will focus on the binding of particles, ranging in size between a few up to hundred nanometers, which are covered with small ligands. Using coarse grained simulations the importance of particle clustering, geometry and flexibility will be studied.
A key protein in primary hemostasis is the von Willebrand factor (VWF), a large multimeric protein present in blood. Our research aims to unravel the regulatory role of shear stress in the maintenance of the sensitive equilibrium of VWF activation, VWF-mediated adhesion, and its degradation in primary hemostasis. We investigate a coarse-grained polymer model and employ hydrodynamic simulations based on the Langevin equation supplemented by hydrodynamic interactions and scaling arguments to get a conceptual picture of different functional and structural control mechanisms in the VWF system. In particular, we analyze in detail the dynamics and the adsorption behavior of collapsed polymers in shear flow using different types of surfaces and different binding models.
Besides including interesting aspects of non-equilibrium hydrodynamics, our research is a further step in understanding novel binding mechanisms in biological systems like the counterintuitive phenomenon of shear-induced adhesion.