Protein and Inhibitor Design

 

The combination of structural biology and generative AI methods (awarded the Chemistry Nobel Prize in 2024) is a powerful tool for drug design and protein engineering. We have several ongoing  projects addressing these issues, including the structure determination of a snake toxin (α-corbatoxin, which inhibits the nicotinic acetylcholine receptor) bound to a peptide inhibitor identified by phage display. We are also part of a study for the development of an antibiotic targeting an essential enzyme in Mycobacterium tuberculosis, also involving the use crystallographic fragment screening. To improve biological research tools for biotechnology applications, we have crystallized optimized proteins and enzymes with an altered substrate spectrum with the goal to provide structural information for further development based on rational design. Recent efforts focus on the De novo design of "AI binders" as spatio-temporal probes for cellular GTPase activity. 

Mitton-Fry RM et al. (2025)
Structure-guided engineering of a polyphosphate kinase 2 class III from an Erysipelotrichaceae bacterium to produce base-modified purine nucleotides.
RSC Chem Biol doi.org/10.1039/d5cb00108k

Humberg C. et al. (2025)
A Cysteine-Less and Ultra-Fast Split Intein Rationally Engineered from Being Aggregation-Prone to Highly Efficient in Protein trans-Splicing.
Nat Commun doi.org/10.1038/s41467-025-57596-x.

Füsser F.T et al. (2023)
Novel starting points for fragment-based drug design in Mycobacterial Thioredoxin reductase using crystallographic fragment screening.
Acta Crystallogr D Struct Biol doi: 10.1107/S2059798323005223

Lynagh et al. (2020)
Peptide Inhibitors of the α-Cobratoxin-Nicotinic Acetylcholine Receptor Interaction.
J Med Chem doi: 10.1021/acs.jmedchem.0c01202