Welcome to the website of the Müller research group!
Molecular conformation – the arrangement of the atoms of a flexible molecule in space – is central to the functioning of biomolecules, impacts the efficacy of drugs, and prominently figures in the explanation of several neurodegenerative diseases. Understanding the competition between the multitude of noncovalent, through-space interactions that determine molecular conformation is essential, for instance, to rational drug design, and molecular recognition in host-guest chemistry.
Our research centers on a systematic bottom-up study of intra- and intermolecular interactions stabilizing the conformational structures of biological building blocks. We use molecular beam single-conformation spectroscopy to disentangle the UV, IR, and Raman spectra of single conformational structures of, for instance, small cyclic peptides, neuraminidase inhibitor analogs, and active drug metabolites. In so doing, we combine laser spectroscopic UV-UV, IR-UV, and Raman-UV double-resonance techniques with mass spectrometric ion detection to record conformation-specific UV, IR, and Raman spectra. Assigning these spectra with density functional calculations based on molecular dynamics conformational searches, we arrive at specific conformational structures that are submitted to further analysis. In collaboration with the group of Prof. Timothy S. Zwier (Purdue University), we currently develop electrostatic models for peptide secondary structure determination based on single-conformation infrared spectra in the amide I/II region. In the long term, one of our goals is to extract atomic properties from our experimentally determined conformational structures for the experiment-based improvement of multipole force fields.
A special focus of our work is the microsolvation of biomolecular building blocks. Using our arsenal of double-resonance techniques, we determine single-isomer structures of solute-solvent clusters. The goal of this line of research is to quantitatively characterize the competing intra- and intermolecular interactions, especially between functional groups containing sulfur and nitrogen atoms. We try to answer questions such as: How many solvent molecules does it take to make a zwitterion more stable than the neutral form? What are the preferred solvent interaction sites of a solute containing different functional groups? In what kind of interactions do these functional groups engage with "first solvation shell" solvent molecules? In what way does the solute conformational structure change upon adding an increasing number of solvent molecules? Our ultimate goal is to develop physical models that bridge the “solvation complexity gap” between isolated molecules on the one hand and bulk-solvated molecules on the other hand, and that allow, for instance, to quantitatively predict intermolecular interaction-induced vibrational frequency shifts.
The Mueller group is embedded in the newly established Cluster of Excellence RESOLV (Ruhr Explores Solvation) of the German Research Foundation (DFG). We have running collaborations with a number of groups within the Cluster. To learn more about our research, please follow the links on the menu on the upper left or click on the picture below.