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In our lab we apply a broad range of computational tools to a variety of research projects including small molecule drug discovery, protein modelling, and the design of novel gene therapy approaches.
Drug design
As computational chemists working in the field of computer-aided drug design, we have a strong interest in identifying, analyzing, and optimizing novel bioactive compounds for different targets and target classes. For this purpose, we have access to state-of-the-art molecular modelling, virtual screening, and cheminformatics software packages.
Cancer drug resistance
One of the main mechanisms conferring resistance to targeted cancer drugs is mutation of the drug target. Early knowledge about clinically relevant resistance mutations is critical, as it allows us to proactively streamline our drug discovery efforts and to provide effective treatment alternatives as soon as the resistance clones emerge in patients. We have developed a computational workflow (Kaserer & Blagg, cell Chem. Biol. 2018) systematically evaluating all possible mutations in close proximity to the ligands, to prioritize mutations that are likely to arise in patients.
Our research aims to improve and extend this workflow, e.g. by including mutations distant from the binding site and compounds, for which experimental structural data is lacking. Together with our collaboration partners, we prospectively apply the existing workflow to molecules, which have only recently been approved or which are currently investigated in clinical trials, and for which data regarding resistance mutations are not available yet.
Protein design
Besides deleterious effects, mutations can be introduced intentionally to alter the function and properties of proteins as required. We apply computational methods for the rational structure-based design of novel and custom-tailored proteins for gene therapy approaches. In close collaboration with experimental scientists, we work on novel strategies to tackle chronic pain, treatment-resistant epilepsy, and neurodegenerative disorders such as Parkinson’s disease.