Research in the Brenk lab

The overall research goal of the Brenk lab is to improve methods used for structure-based drug design and to apply these methods to design inhibitors for enzymes with biological relevance. A key point in our research is the interplay of theoretical and experimental methods.

Banner Brenk Lab
Photo: Ruth Brenk

Research topics

(Disclaimer: The university does not allow me to adjust the width of the figures. I know the page looks a bit ugly when you look at it at the PC, but there is nothing I can do about this.)

Currently, we are working on the following topics:

1. RNA-ligand interactions

We are developing methods to predict the binding modes and affinities of RNA-ligand complexes and the druggabilty of RNA targets. Further, we are exploiting these methods to discover ligands for riboswitches which are novel targets for antibiotics.

Binding site of the TPP riboswitch
Binding site of the TPP riboswitch. Photo: Ruth Brenk

Related News pages:

Selected publications:

  1. Hübenthal, A.; Panchal, V.; Brenk, R.; Mack, M. Functional Analysis of Thiamine Pyrophosphate-Responsive Riboswitches in Human Bacterial Pathogens of the ESKAPE Group Using a Dual-Luciferase Reporter Gene Assay. J Bacteriol 2025. [DOI (external link)]
  2. Panchal, V.; Husmann, J.-Å.; Günther, K.; Zeeshan, M.; Haug, B. E.; Brenk, R. Discovery of RNA-Binding Fragments Using Biolayer Interferometry. RSC Medicinal Chemistry 2025. [DOI (external link)]
  3. Rekand, I. H.; Brenk, R. DrugPred_RNA-A Tool for Structure-Based Druggability Predictions for RNA Binding Sites. J Chem Inf Model 2021.[Pubmed (external link)]|[DOI (external link)]
  4. Lundquist, K. P.; Panchal, V.; Gotfredsen, C. H.; Brenk, R.; Clausen, M. H. Fragment-Based Drug Discovery for RNA Targets. ChemMedChem 2021. [Pubmed (external link)]|[DOI (external link)]
  5. Daldrop P, Reyes FE, Robinson DA, Hammond CM, Lilley DM, Batey RT, Brenk R. Novel Ligands for a Purine Riboswitch discovered by RNA-Ligand Docking. Chem Biol 18 (3), 324-35 (2011). [Pubmed (external link) | DOI (external link)]
  6. Rekand IH, Brenk R. Ligand design for riboswitches, an emerging target class for novel antibiotics. Future Med Chem. 2017 Sep;9(14):1649-1662. [Pubmed (external link) | DOI (external link)| Post-print version]
  7. Wehler, T.; Brenk, R. Structure-Based Discovery of Small Molecules Binding to RNA. In RNA Therapeutics; Topics in Medicinal Chemistry; Springer, 2017; pp 47–77. [DOI (external link)]

2. A better understanding of protein-ligand interactions

Ideally, we should be able to predict the binding affinity of a ligand based on the structure of the protein-ligand complex. However, we are still far away from reaching this goal. Therefore, we are using a combination of biophysical and computational methods to improve our understanding of protein-ligand interactions. A particular focus in this context is to better undertand the driving forces of selective inhibiton in highly conserved binding sites. In addition, we are developing methods to predict how likely it is to to find a drug-like ligand for a given binding site and which physico-chemical properties this ligand will likely have. Further, we are exploiting the vast data about protein-ligand complexes to validate and develop scoring functions to predict the binding affinities of ligands to their targets. For this task, we are using modern machine learning methods.

An empty protin binding site with a question mark.
Which ligand could fit into this pocket? Photo: Ruth Brenk

Related News pages:

Selected publications:

  1. Schuck, B.; Brenk, R. On the Hunt for Metalloenzyme Inhibitors: Investigating the Presence of Metal-Coordinating Compounds in Screening Libraries and Chemical Spaces. Archiv der Pharmazie, e2300648. [DOI (external link)|ChemRvix] (external link)
  2. Kersten C, Fleischer E, Kehrein J, Borek C, Jaenicke E, Sotriffer C, Brenk R. How To Design Selective Ligands for Highly Conserved Binding Sites: A Case Study Using N-Myristoyltransferases as a Model System. J Med Chem. J Med Chem. 2020 Mar 12;63(5):2095-2113 [Pubmed (external link) | DOI (external link)]
  3. Sarkar A, Brenk R. To Hit or Not to Hit, That Is the Question - Genome-wide Structure-Based Druggability Predictions for Pseudomonas aeruginosa Proteins. PLoS One 10 (9), e0137279 (2015). [Pubmed (external link) | DOI (external link)]
  4. Krasowski A, Muthas D, Sarkar A, Schmitt S, Brenk R. DrugPred: A Structure-Based Approach To Predict Protein Druggability Developed Using an Extensive Nonredundant Data Set. J Chem Inf Model 51 (11), 2829-42 (2011). [Pubmed (external link) | DOI (external link)]

3. Structure-based ligand design

In collaboration with other labs we are working on the structure-based design of ligands for a variety of targets. A particular focus of this work is the discovery of starting points for new antibiotics.

Fragment hits binding to FabF.
Fragment hits binding to FabF. Photo: Ruth Brenk

Related News pages:

Selected publications:

  1. Georgiou, C.; Espeland, L. O.; Bukya, H.; Yadrykhins’ky, V.; Haug, B. E.; Mainkar, P. S.; Brenk, R. Towards New Antibiotics: P. Aeruginosa FabF Ligands Discovered by Crystallographic Fragment Screening Followed by Hit Expansion. European Journal of Medicinal Chemistry 2025, 117563. [DOI (external link)].
  2. Jalencas, X.; Berg, H.; Espeland, L. O.; Sreeramulu, S.; Kinnen, F.; Richter, C.; Georgiou, C.; Yadrykhinsky, V.; Specker, E.; Jaudzems, K.; Miletić, T.; Harmel, R.; Gribbon, P.; Schwalbe, H.; Brenk, R.; Jirgensons, A.; Zaliani, A.; Mestres, J. Design, Quality and Validation of the EU-OPENSCREEN Fragment Library Poised to a High-Throughput Screening Collection. RSC Med. Chem. 2024. [DOI (external link)|PractialFragments (external link)].
  3. Espeland, L. O.; Georgiou, C.; Klein, R.; Bhukya, H.; Haug, B. E.; Underhaug, J.; Mainkar, P. S.; Brenk, R. An Experimental Toolbox for Structure-Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics. ChemMedChem 2021. [Pubmed (external link)]|[DOI (external link)]
  4. Klein R, Cendron L, Montanari M, Bellio P, Celenza G, Maso L, Tondi D, Brenk R. Targeting the Class A Carbapenemase GES-5 via Virtual Screening. Biomolecules. 2020 Feb 14;10(2). pii: E304.[Pubmed (external link) | DOI (external link)]
  5. Frearson JA, Brand S, McElroy SP, Cleghorn LA, Smid O, Stojanovski L, Price HP, Guther ML, Torrie LS, Robinson DA, Hallyburton I, Mpamhanga CP, Brannigan JA, Wilkinson AJ, Hodgkinson M, Hui R, Qiu W, Raimi OG, van Aalten DM, Brenk R, Gilbert IH, Read KD, Fairlamb AH, Ferguson MA, Smith DF, Wyatt PG. N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature 464 (7289), 728-32 (2010). [Pubmed (external link) | DOI (external link) | F1000 recommended (external link)]
Last updated: 11.02.2026