Research in the Theoretical Molecular Biophysics group is focused on improving our understanding of the molecular mechanisms by which proteins carry out their biological function. Our studies involve both individual proteins and larger macromolecular assemblies, and the type of processes we investigate range from ligand binding to conformational change. Our primary approach is computational, physics-based and structurally oriented. All of which means that we like to employ state-of-the-art, computationally-intensive molecular simulation methods to analyze the dynamics and energetics of the molecular systems under study.
Because our expertise is primarily theoretical and computational, it is of crucial importance for us to work in close collaboration with experimentalists, particularly in the areas of structural biology, biochemistry and molecular biophysics. Fortunately, the Riedberg Campus in Frankfurt am Main provides a highly interdisciplinary, international environment from which we benefit greatly - in addition to our interactions with groups located elsewhere in Europe and abroad. The following is a brief description of our research interests.
Mechanisms of recognition and signaling at the immunological synapse
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Designated cells in our adaptive immune system are able to display on their surface protein fragments or lipids belonging to foreign organisms, such as bacteria or viruses. These foreign antigens can be then recognized by special lymphocytes called T-cells; the transient interface formed between an antigen-presenting cell and a T-cell is known as the immunological synapse. Upon recognition of foreign antigens, a chemical signal is generated at the membrane of the T-cell and transmitted towards its interior. These activating signals ultimately translate into diverse biochemical responses that protect us from infection.
A great diversity of proteins contribute to the formation of the immunological synapse and the subsequent signaling process. These include antigen-binding proteins, membrane receptors, scaffolding proteins, tyrosine kinases, and even ion channels. The immunological synapse thus encompasses many of the processes mediated by proteins in all forms of life, from substrate recognition to allostery and conformation change to membrane permeation. This area is therefore an important focus of our research.
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Modular protein domains
The transmission of information within cells requires the organization of a diverse range of proteins into coherent interaction networks. Spatially, this requires the transient formation of macromolecular complexes, so as to allow the relay of chemical signals from protein to protein. So-called modular protein domains play a fundamental role in the dynamic scaffolding of these signaling complexes. These small modules can act as promoters or inhibitors of the interaction between protein partners within a network, thus regulating the transduction of signals. A good overview of the structure and function of these modules can be found for example following this link.
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The versatility of modular domains is in part conferred by their own ability to self-organize into multi-modular constructs, which may adopt alternate arrangements with distinct binding properties. Furthermore, individual modular domains can also adopt multiple conformations in response to environmental stimuli. Both these aspects - self-organization and conformational exchange - are of great interest in our group.
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Molecular mechanisms of membrane protein function
Proteins embedded in or associated with biological membranes are of essential importance - they mediate a wide range of processes such as the communication between and within cells, the import and metabolism of nutrients, etc. Membrane proteins have also great potential for biotechnological applications and as pharmaceutical targets.
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A major focus of the research work carried out at the Max Planck Institute of Biophysics and at the University of Frankfurt pertains membrane protein function. Accordingly, our group is involved in several interesting collaborations in this area; one example is the family of ATP synthases, that is, enzymes that are able to produce ATP - an important source of energy for all biological systems.
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