We are excited to share the latest news on the progress of the first BioSolveIT Drugathon 2022. With the goal to discover novel antibiotics for the target 1-deoxy-d-xylulose 5-phosphate synthase (DXPS), users enjoyed BioSolveIT applications to design and optimize their compounds with thiamine pyrophosphate (TPP) as starting point. Fragments were grown, scaffolds were replaced, ideas docked — and tangible compounds were retrieved from huge Chemical Spaces with infiniSee.
Imagine: We received more than seven thousand compounds from over four hundred participants and the scientific community within the 24 hours of the event!
As follow-up of the event, submissions were internally reevaluated: Compounds were redocked into DXPS using the FlexX, and poses were assessed with the HYDE scoring algorithm (both part of the drug discovery dashboard SeeSAR). To increase the likelihood of success, proposed compounds were docked into an ensemble of target structures (with and without water molecules, apo state, considering a magnesium ion etc.). Visual inspection of compounds with favorable pose parameters (HYDE affinity score, molecular torsions, inter- and intramolecular clashes) led to a selection of candidates. Additionally, we decided to check for unique and promising scaffolds suggested by the community as replacement for the pyrimidine moiety of the TPP and extracted those for the next step.
To further expand the hunting grounds and to increase the chemical diversity of the results, our partners’ make-on-demand Chemical Spaces were screened for accessible compounds containing promising scaffolds. The retrieved 1,000,000 compounds were subsequently docked and scored. The best candidates in compliance to the aforementioned pose parameters were visually inspected and selected for purchase.
As for the next stage, the acquired compound set will be experimentally tested in collaboration with the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and the Hirsch Group. We will keep you updated on the results and are looking forward to the outcomes of this amazing event.
We are also excited to announce this year’s Drugathon 2023: Save the date, it is August 2nd/3rd 2023 with 24 hours of drug discovery with researchers around the world!
The Drugathon is a BioSolveIT event in which participants work together for 24 hours on a drug discovery project. BioSolveIT supports the community with software, and funds resources to purchase and synthesize the compounds with the best predicted affinity among the suggestions submitted by the community. You can read more about the 2022 event here.