Another Kind of Drug Design Training and Research

The eChemInfo Training and Innovation Course in Drug Design took place in Milano on 17-21 July 2017. EChemInfo workshops are organized for almost 10 years. However, we re-invented them somewhat when we moved to Milano last year and optimized the concept this year. Our workshops were always based on case studies. Besides the presentations of different techniques ranging from homology modelling, ligand- and structure- based design, molecular dynamics simulations as well as toxicity predictions and QSAR/QSPR modellling, group work sessions were included in the program to directly use the methods hands-on. Resulting out of the Synergy project and the Scientists against Malaria initiative, real data from a study investigating the druggability of a plasmodium kinase and identification of inhibitors were provided as a test bed for the methods presented by the speakers. Each year, new results were generated by the participants e,g, by adding new ligands into the library of tested compounds, use alignment techniques and/or docking to predict actives and verify these with more advanced methods like MM-GBSA. Even if this had the potential to become a way to do collaborative, community-driven research bringing in expertise from different places whenever it is needed but also transfer the knowhow to young researchers to give them the ability to take over the task, the continuation of the Malaria project and follow-ups of the work performed at the workshop proofed to be complicated since all participants had to continue the work on their own projects once they were back at their home institution.  

Since we didn’t want to abandon the concept of the case studies, since working with real data made the hand-on sessions more interesting and also revealed the limitations and pitfalls of the methods better compared to examples taken from carefully prepared tutorials encouraging the participants to critically analyse the obtained results, we invented the concept of “bring your own problems”. Instead of one specific case study chosen by the organizer, every participant was invited to define her/his own case study based on their work. The presentations of the different approaches including their applicability domain and highlighting areas which need special considerations were concentrated more in the first half of the training week. In this way, methods useful for a specific case study could be identified early. As a premiere this year, sessions on medium-throughput crystallography and NMR techniques for fragment-based design providing the input for the modelling methods as well as an industry perspective was added to the program. In the second half of the week, the program was mainly filled with hands-on sessions. Breakout groups were formed, in which groups of participants and speakers developed new ideas for research directions for the case studies. Participants interested in a specific methods grouped around the expert in this area and discussed the best usage and in many cases started to generate input files and producing the first results. This was possible due to the commitment of the speakers to not only arrive just for their talk and then leave directly after it but to stay for multiple days and in many cases even for the complete week. Besides leading the groups in the break-out sessions, they were, in this way, also able to participate in the discussion of additional sessions and provide personal experiences with respect to adaptations needed for specific systems and alternatives if a standard method fails to provide the desired results or accuracy. We will continue to even more strengthen these aspects of the workshop in the following years.

Even if the workshop is now over, we hope that we could build the foundation for ongoing activities of this year’s and future groups. The speakers are all committed to continue to follow the case studies and provide additional input regarding suitable methods and practically support for generating the necessary input files and performing the analysis of the results. Additionally, with the new contacts to participants with different scientific background formed during the workshop, we hope that this support will more and more be given by other former participants acquiring additional expertise during their ongoing carriere finally resulting in a culture of collaborative research and community-driven innovation. The next months and years will show if we can establish a working community or if or how we have to adapt the concept to keep up the momentum. If you have ideas, we would be very thrilled to hear about them.