The Avalanche Tool for Virtual Screening and Property Prediction
Screen snapshots from Avalanche: Step 1 (left) Input query panel; Step 2 (right) View of hit list from search, detailed property browser, and 3D alignment of query and hit molecule.
The biopharmaceutical industry, as well as companies that serve this enterprise, routinely use virtual screening in drug discovery campaigns to find molecules in a chemical database that are similar to a query compound. This process is intended to generate new drug leads and, subsequently, new intellectual property. However, current virtual screening methods are generally unable to identify truly novel scaffolds that represent less populated regions of chemical space and patent space.
In response, Snowdon is developing a new ligand-based virtual screening tool called Avalanche that employs both shape- and pharmacophore-based comparison with 3D alignment to compare the query molecule with test compounds residing in a chemical compound collection. Avalanche excels at scaffold hopping, since it uniquely matches molecules based on 3D shape and pharmacophoric surface features (donor, acceptor, hydrophobic, +/- charge, etc.) rather than on chemical structure. Avalanche proceeds in two fast, automated steps: Initial shape/pharmacophore based comparison, followed by 3D alignment of the top hits which are scored, re-ranked and presented to the user for further visualization and evaluation.
By seamlessly combining molecular shape and surface features with 3D alignment, Avalanche enhances the chances of success finding more biologically relevant hits and leads that would be missed by common substructure-based or fingerprint-based virtual screening methods. Convenient access to the full capabilities of Avalanche is provided by a flexible, intuitive, and user-friendly interface either locally or remotely via cloud implementation. Ongoing efforts are aimed to extend Avalanche as a predictor of key properties associated with early-stage drug discovery and development such as ADME/Tox endpoints, protein target and off-targets, and alternative dosage forms.