Sibylla's innovative pharmacological platform is aimed at discovering new drugs for untreatable diseases by identifying protein degraders that act by interfering with the folding pathway of the target protein. This approach is named PPI-FIT that stands for Pharmacological Protein Inactivation by Folding Intermediate Targeting. The range of druggable targets is currently estimated to be approximately 15% of the human proteome. PPI-FIT enables to widen this range by allowing the identification of druggable pockets on protein folding intermediates. The availability of increasingly larger chemical libraries presents great drug discovery opportunities. Therefore, we are developing a virtual screening protocol that can rapidly and accurately evaluate billions of candidate ligands' binding modes towards the identified binding pocket by adopting a hybrid Ligand and Structure-Based approach. This protocol will be able to screen billions of compounds through ligand-based methods while computing the binding affinity with structure-based techniques, only for a subset of the complete library. ChemAxon's tools enable our ligand preparation procedures for structure-based modeling. Moreover, ChemAxon's physicochemical properties calculators are important for the molecular featurization procedures used in our machine learning models' development pipeline.