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.
