It is our greatest pleasure to announce the winner of the Fall 2024 edition of the Scientific Challenge: the winner is Shafi Ullah Khan from the Université de Caen Normandie – ANTICIPE (Caen, France) with his project ‘Structure-Based Design of Novel UBE2N Inhibitors to Overcome PARP Inhibitor Resistance’.
Focusing on the critical clinical challenge of PARP inhibitor (PARPi) resistance in ovarian cancer, Shafi Ullah developed a strategic Structure-Based Drug Design (SBDD) workflow to target UBE2N. The project utilized an integrated computational approach, beginning with Ligand-Based Virtual Screening (LBVS) across five massive commercial databases (including REAL Space and GalaXi). By exploring an immense Chemical Space of approximately 5 trillion compounds, an initial pool of 2,500 unique potential hits was successfully identified.
A standout feature of this research was the detailed structural analysis of the UBE2N protein. Using the Unoccupied pocket tool in SeeSAR, Shafi Ullah identified three distinct and previously unexplored binding pockets near the critical Cys87 residue. Following Structure-Based Virtual Screening (SBVS) and HYDE assessment, the most promising candidates were further optimized using the FastGrow Inspirator and ADME assessments. To ensure high translatability and minimize false positives, 25 selected leads were subjected to 100ns Molecular Dynamics (MD) simulations for rigorous validation.
Overall, Shafi Ullah impressed us with the sheer scale of the virtual screening and the innovative identification of novel binding sites to tackle drug resistance. This systematic progression from massive library screening to specific pocket exploration and MD validation is what earned Shafi Ullah the scientific award for both project depth and execution. We are excited to see the final candidates move forward to wet lab validation and cell-based assays.
We wish Shafi Ullah all the best for his professional and scientific future and look forward to reading more about his discoveries in the future!
You can read about the full project and the achieved milestones following this link.