Computer-Assisted Drug Design

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Molecular modeling meets medicinal chemistry. Students of different disciplines jointly solve a molecular design challenge inspired by real-life industrial drug discovery. This workshop offers participants the experience of solving a complex scientific problem and succeed as a team.

The Computer-Assisted Drug Design class challenges the students with a difficult task inspired by real-life projects. This task can be solved in many different ways, depending on the decisions of the students. The course is organized as a two-week workshop and is divided into a theoretical (computational) part and an experimental part. In addition to offering training in the methodology of modern drug discovery, it provides a unique teamwork experience. The first week of the workshop lays the foundation for the computational part by providing students with the necessary information through lectures and software tutorials. The second week comprises hands-on “wet” experiments, allowing the students to synthesize the molecules they themselves designed. The students form small competing “companies” and are confronted with the mission to computationally design, chemically synthesize and biochemically test compounds for their ability to inhibit the activity of a pharmacologically relevant enzyme.

Solving this complex problem requires transdisciplinary thinking and team spirit. While conventional lectures and seminars are useful for transmitting in-depth scientific knowledge, we saw the necessity to teach students how to “think outside the box”. This is an essential skill to successfully address the challenges in drug discovery. We developed the concept of this workshop, including the idea of forming virtual competing companies, to better teach students the skills necessary for drug discovery. The challenge revolves around a central aspect of learning, namely to take personal responsibility for one’s learning. The teams/companies are free in their choice of approaches how to design their molecules. Rather than focusing on the students trying to find some predefined solutions, we motivate the participants to actively argue for their choices and compare their decisions. This also includes taking responsibility for the decisions that were made and the actions taken.

Generous support from ETH Innovedum allowed us to “re-invent” education in computational drug design. We implemented a game-like Moodle challenge, accompanying the practical classes and the lectures. Via Moodle the students have the opportunity to independently access the questions and advance to different levels based on their individual performance. We also make use of Microsoft’s HoloLens to explain the concept of a molecule’s solvent-accessible surface via mixed reality. For this purpose, we conceived the Molegram App in collaboration with the LET (ETH) and the company afca AG.

The concept of this teaching initiative was developed by Prof. Dr. Gisbert Schneider and Dr. Jan Hiss and is continuously refined with support by the other members of the Molecular Design Laboratory (MODLAB). All members of the group support the implementation and supervision of the class. The workshop is part of a series of classes in Computer-Assisted Drug Design. As an elective subject of the MSc curricula offered by the Institute of Pharmaceutical Sciences it is open to interested participants from all departments of ETH.

The students participating in the project become increasingly fascinated with computational approaches and applying them to molecular design problems. The less computer-savvy participants lose their fear of failure and become aware of the value they add to a mixed team of scientists. We have also recognized an increased interest amongst the workshop participants for joining our research group. Furthermore, the students obviously enjoy being given the opportunity to make and defend their own choices. Presenting the companies’ results as a team in front of the other participants helps the students overcome the fear of giving a talk. Being responsible for one’s own choices fosters teamwork, leads to a strong identification with the project, and enables critical reflection. Arguing with your fellow student as to why a certain method may be useful, rather than simply repeating the teacher’s statements is a great opportunity for learning. This personal involvement and the opportunity to discuss scientific problems with the teacher at the same level strengthen self-assurance and the ability to take responsibility for one’s actions at the same time.