This Group

Tobias Brinkjost

Education

  • Ph.D. in Natural Science
  • Dipl. Computer Scientist
  • Focus on Algorithm Engineering

ORCID

Besides Science

  • Playing drums
  • Cycling
  • Acting

Christiane Ehrt

Education

  • Ph.D. in Natural Science
  • M.Sc. Bio Chemistry
  • Focus on Protein Structure and Protein-Ligand Interactions

ORCID

Besides Science

  • Literature
  • Irish Language
  • Gardening

Our Story

In 2012, three new junior groups were founded at the Faculty of Chemistry and Chemical Biology of the TU Dortmund University. It was about the same time Tobias finished his studies as a computer scientist. While he was seeking for new challenges, his former supervisor called his attention to one of these junior groups which focused on rational drug design. He was offered a Ph.D. position to investigate the applicability of a hypothesis for which no automated approach had been available. Only the development of an automated method could verify this hypothesis. As an algorithm engineer, it was impossible for him to refuse such a challenge, and he became the first Ph.D. student of this group.

The abovementioned concept is also referred to as ligand-sensing cores, proposed by Koch and Waldmann [1]. The authors proposed that similar arrangements of secondary structure elements (SSEs) in the neighborhood of a ligand binding site (ligand-sensing core) can recognize similar scaffolds in disregard of the overall fold. 2013 went by and led to the development and implementation of the overall workflow and the first data structures to represent the geometric arrangement of SSEs. In 2014, Christiane finished her studies in biochemistry and joined the group to broaden her experience in computer-based modelling. She intended to investigate protein-ligand interactions in general, and the identification of new hits for the inhibition of trypanothion synthase (TryS) from a computational point of view.

As we both joined this group for the same reasons, to challenge our frontiers by the unknown, we teamed up for the hunt for ligand-sensing cores. Our different perspectives lead to a fruitful synergy based on inquisitive discussions to elaborate what is possible in each of our scientific origins.

After two years of research on ligand-sensing cores, no evidence for or against the hypothesis could be given. Not being able to derive any conclusion was unsatisfying for both of us. This particular moment was the initial spark that lead to the dedication to the research of SSEs in a much broader sense.

We started to dig deep and scrutinized all of our assumptions we had initially taken for granted. In other words, we opened a lucky bag. We found more than 30 different ways to assign SSEs based on atomic protein structures, although their assignment is usually performed using the DSSP algorithm by Kabsch & Sander [2]. In addition, SSEs are oftentimes regarded as fixed structures, the contrary is the case.

Our Mission

We are driven by passion and curiosity to investigate the classification, elaboration, and application of SSEs. We want to establish the awareness that there is more to SSEs than being accepted as given for the visualization of protein structures in pretty pictures. We are eager to question concepts that are taken as granted. We strive for comprehensible and reproducible facts and proofs in contrast to believe or obfuscation. Finally, we share our results, experiences, and knowledge and welcome discussions and collaborations to foster an open scientific community.

Our first published method, SCOT, demonstrates this way of doing research and our ideas behind the role of SSEs in protein structures. More ideas are about to come.

Our Dream

On the one hand, the results of our synergy provided answers to many formerly open questions. On the other and, it nourished our curiosity, broadened our view, and, in consequence, led to numerous new questions, ideas, filled white-boards, and projects.

If granted three wishes as it only happens in fairy tales, one would definitely be to pursue our research independently and honestly in the future. In a dedicated research group, this would certainly foster our understanding of yet unanswered questions.

References

Bibliography

  1. M. A. Koch and H. Waldmann. Protein structure similarity clustering and natural product structure as guiding principles in drug discovery. In: Drug Discovery Today 10.7 (2005), pp. 471–483. DOI: 10.1016/S1359-6446(05)03419-7.
  2. W. Kabsch and C. Sander. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. In: Biopolymers 22.12 (1983), pp. 2577–2637. DOI: 10.1002/bip.360221211.