EUROPIN Summer School on Drug Design 2025
Date & Time - September 14th-19th, 2025
Location - Vienna, Austria
Schrödinger is excited to be participating in the EUROPIN Summer School on Drug Design 2025 conference taking place on September 14th – 19th in Vienna, Austria. Join us for a presentation and workshops by Daniel Cappel, Senior Principal Scientist at Schrödinger.
SEPT 16 | 14:00 A novel workflow for the in silico identification and prioritization of potential allosteric binding sites based on mixed solvent simulations and SiteMap
Speaker:
Daniel Cappel, Senior Principal Scientist, Schrödinger
Abstract:
Allosteric modulation is a promising strategy for developing drugs against difficult targets where traditional orthosteric site targeting faces challenges with selectivity, resistance, or developability. The increasing availability of high-resolution protein structures and advancements in computational power and in silico algorithms have expanded the potential of structure-based drug design (SBDD) for allosteric drug discovery. However, there remains a significant need for effective tools to identify and prioritize potential allosteric binding sites, particularly those not accessible in the apo protein structure. To address this, we have developed a novel workflow that leverages mixed solvent molecular dynamics (MxMD) simulations to reveal potential binding sites, coupled with an improved SiteMap for scoring the druggability of these sites. Our combined approach achieved a >80% top 5 found rate of known allosteric binding sites in apo structures from a set of 22 apo/holo PDBs, compared to only 63% with SiteMap alone and 54% with MxMD alone. We further evaluated our workflow on a curated set of five pharmaceutically relevant targets with multiple known allosteric binding sites, and our method outperformed popular machine learning methods, p2rank and DiffDock, as well as SiteMap, in all systems except one. Finally, we report the successful application of this workflow to an active drug discovery project within our therapeutics group. Our new workflow offers an improved method for characterizing binding sites in allosteric systems. Furthermore, efforts are underway to refine the predicted binding sites to enable virtual screening campaigns. This combined approach demonstrates a significant improvement over existing methods for identifying allosteric binding sites and has the potential to enable effective hit discovery campaigns for novel binding sites.
SEPT 16 | 14:30 A beginner’s guide to system preparation, docking and designing ligands
Speaker:
Daniel Cappel, Senior Principal Scientist, Schrödinger
Abstract:
If you are interested in learning to navigate the Schrödinger suite and how to perform docking of small molecules, join us for a hands-on workshop designed for beginners. The main Maestro interface houses all the tools that are required to bring in your starting small molecules and protein system, so that they may be prepared correctly. Once you are comfortable with the fundamentals of preparing your raw materials, we will move on to understanding more about the binding site and its features, which will help us think about how a ligand might interact with it. This forms a fundamental basis for understanding our docking results, so we will start by setting up and running docking jobs and analyzing how the resulting docked compounds fulfill the basic criteria of shape and molecular interactions that lead to the final scoring term. Finally, we will explore ligand design in a more automated fashion using the Ligand Designer GUI which facilitates on-the-fly ideation through ‘build and dock’ workflows. Using embedded libraries of building-blocks, users can modify their initial idea in many intuitive ways: from attachment points on the bound ligand; the free and viable space in the binding site; through picking specific residues in the protein or specific waters in the binding cavity to guide the design process.
SEPT 17 | 14:30 Efficient virtual screening: Combining ligand-based screening with QuickShape and advanced water-based scoring with WaterMap and GlideWS
Speaker:
Daniel Cappel, Senior Principal Scientist, Schrödinger
Abstract:
In this workshop, we will assemble a modern virtual screening pipeline from start to finish. We will curate a tailored screening library by simultaneously querying catalogs of many vendors. Using QuickShape screening, we will efficiently prioritize compounds for molecular docking, reducing computational cost and focusing on promising candidates. Then, we will perform compound selection leveraging chemical properties, pharmacophore features, and diversity analysis with the Hit Analyzer tool in Maestro to identify a diverse set of potential hits. Using GlideWS, we will rescore these compounds and use the advanced visualizer in Maestro to eliminate likely false positives by analyzing protein desolvation, improving the accuracy of your screening results. Finally, we will nominate a selection of top-ranking compounds for sophisticated AB-FEP+ rescoring.
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