Forschung
Structure-based computational approaches applied to rational engineering and de novo design for target/drug discovery and biotechnology innovation.
Rational engineering and de novo design for biotechnological and medical applications:
- De novo rational design of molecular scaffolds mimicking protein interactions for specific interference in cell signaling processes
We apply molecular modelling and computer simulation techniques to design molecules of pharmacological and biotechnological interest. We make use of scaffolds found in nature and rationally modify them to enhance properties such as stability, affinity and specificity. In parallel, we de novo design scaffolds that mimic natural protein 3D templates involved in pharmacologically relevant interactions.
- Rational engineering of biomaterials for tissue regeneration
GAGs (glycosaminoglycans) are common constituents of cell surfaces and extracellular matrices, and their interactions with a wide variety of molecules such as growth factors and cytokines play a prominent role in basic biological phenomena like cell adhesion, migration, proliferation and differentiation. Thanks to these biocharacteristics, attachment of GAGs to biomaterials offers a great opportunity to modulate tissue response and create an appropriate environment for cellular signalling, both important issues in tissue engineering and regeneration. In close collaboration with experimentalists, we characterize the structural requirements for protein-GAG binding to understand the molecular basis of the affinity and specificity governing these interactions. We apply computational modelling and simulation techniques to address the hetereogeneity of the GAG component and to investigate the structural and physicochemical properties of GAGs in the context of their interaction with biological binding partners. Our studies guide the design of customized GAGs derivatives and matrix scaffolds for regenerative biomaterials aimed at promoting biospecific cell behaviour.
We have succeded in the rational design of new molecules with bone tissue regenerative properties (Biomaterials 2023; 297:122105).
A Sweet Solution to a Cracking Problem: Scientists Design New Bio-Inspired Molecules to Promote Bone Regeneration. https://tud.link/nuxi
Work funded by the German Research Council (DFG; TransRegio 67) and the Federal Ministry of Education and Research (BMBF).
- Rational engineering of enzymes to improve their functional properties
We use structure-based approaches and molecular dynamics simulations to investigate protein–DNA molecular recognition in DNA recombinases and to establish the structural basis of their structure–function relationships. In collaboration with the group of Prof. Buchholz (Med. Fac. TUD), we aim to enable the rational design of recombinases with tailored specificity for diverse DNA target sequences for applications in human genome engineering.
Work funded by the German Research Council (DFG).
- Rational design of inhibitors of the Anaphase Promoting Complex/Cyclosome (APC/C) as leads for drug development
The ubiquitin E3 ligase Anaphase Promoting Complex or Cyclosome (APC/C) is emerging as an attractive drug target in cancer therapy to affect specifically rapidly dividing cancer cells as a first step for gaining specificity in treatment. We use computer-aided molecular design techniques to rationally design molecules inhibiting the APC/C complex and, in close collaboration with the group of Jörg Mansfeld (BIOTEC TUD),biochemical and cell biological approaches are applied to experimentally evaluate the inhibitory potential of our structure-based rationally designed molecules our goal is to obtain potent and specific APC/C inhibitors with optimized properties as lead molecules for drug development for cancer treatment.
We have succeded in the rational design of new small molecules to disrupt cancer growth
(Journal of Medicinal Chemistry 2025; 68(11):11468-11483).
Breaking the cycle: new smolecules to disrupt cancer growth . https://tud.link/6c2qgu
Work funded by the German Research Council (DFG).
Detailed characterization of protein interfaces and implications for protein function and ligand design:
- Comparative analysis of protein-protein and protein-ligand interactions
We develop computational tools for the automated extraction, analysis and classification of protein interaction data within a large-scale, comparative framework. These methods include the detailed characterization of solvent effects in protein recognition. Together, these approaches enable an accurate description of protein interfaces, providing insights into protein function and supporting their application in rational protein and ligand engineering.