ROCS X

ROCS X is OpenEye's (now part of Cadence) next-generation virtual screening solution designed to operate at the trillion-compound scale. Delivered through the Orion® Software-as-a-Service (SaaS) Molecular Design platform, ROCS X is built for computational and medicinal chemists who need to go far beyond commercially available vendor catalogs. By constructing ultra-large 2D and 3D chemical libraries from reaction-informed synthons and intelligently exploring them using active learning, ROCS X enables rapid identification of relevant, synthesizable molecules without requiring full enumeration of intractable chemical spaces.

ROCS X integrates industry-leading tools — OMEGA, ROCS®, and FastROCS — for 3D conformation generation and shape-based similarity search. Using AI-guided sampling via Bayesian bandits, the platform recovers over 95% of top-scoring hits while sampling as little as 0.0002% of a 1.3-trillion-compound library, making it a highly cost-effective and scalable solution for modern drug discovery teams.

Key Features

• Trillion-Scale Virtual Screening: Perform substructure and 3D similarity search on trillions of easily accessible compounds built from curated chemical reactions and purchasable building blocks, far exceeding what is available in vendor databases.
• Reaction-Aware Synthon Libraries: ROCS X generates virtual compounds using curated reactions and a database of readily available reagents, ensuring that identified hit molecules are easily synthesizable.
• Smart Sampling with AI: ROCS X employs Bayesian bandits to efficiently explore product space, recovering high-ranking hits by sampling only a small fraction of the virtual library at low computational cost.
• 3D Shape-Based Search: Leveraging best-in-class FastROCS and ROCS, ROCS X performs accurate 3D similarity scoring using the Tanimoto Combo score (shape overlap plus atom-based overlap) against ligand queries or generic shape queries derived from a protein binding site — enabling searches even in the absence of known ligands.
• Seamless Integration in Orion: Fully integrated into the Orion cloud platform, enabling scalable, on-demand virtual screening workflows from query to hit list.
• Built for Practical Impact: Jointly developed with an industry partner, ROCS X integrates cutting-edge 3D search and AI-guided sampling to accelerate hit discovery beyond vendor catalogs.

Performance and Scientific Approach

• The Tanimoto Combo score quantitatively correlates molecular similarity with the likelihood of comparable biological activity, providing a validated basis for 3D similarity-driven hit identification.
• ROCS X integrates FastROCS (the GPU-accelerated version of ROCS) with a reaction-aware, synthon-based architecture to enable virtual screening of over one trillion synthetically accessible compounds.
• Queries can be derived directly from known ligands or from the complementary properties of a protein binding site, providing flexibility across different discovery scenarios.
• The platform uses query partitioning in synthon space to unlock massive, synthesizable chemical space via substructure and 3D search with physics and AI methods.
• ROCS X efficiently identifies top-scoring, chemically relevant hits while sampling as little as 0.0002% of a 1.3-trillion-compound library, dramatically reducing compute and storage requirements.

Proven Results: Treeline Biosciences

• 150+ novel compounds sourced and synthesized across multiple drug discovery programs.
• Multiple co-crystal structures confirmed, validating 3D ligand-protein interactions.
• High synthetic success rate attributed to the reaction-aware design approach.
• Enabled discovery of hits not found in any vendor catalog.

When to Use ROCS X vs. FastROCS

• Use ROCS X when: you have information about building blocks and reactions in combinatorial chemical space, you want to search beyond billion-size compound databases, or reducing computational cost is a priority.
• Use FastROCS when: you have complete molecular structures for all compounds, you need to perform an exhaustive search of every molecule in the database, or your database size allows full molecular enumeration.

Available Reagents, Reactions, and Ordering

• Building blocks from vendors including Enamine, Molport, and Mcule, combined with more than forty commonly used reactions, provide access to a virtual library of over 1.3 trillion synthesizable compounds.
• Users may also incorporate in-house reagents and reactions into the existing library via available add-ons.
• Customers have used ROCS X to search libraries containing hundreds of trillions of virtual molecules — there is no fixed upper limit on library size.
• Identified hit compounds can be ordered directly from vendors (Enamine, Molport, Mcule) by submitting a quote request with requested structures in SMILES or SD format along with the required quantity.

ROCS X is available as an off-the-shelf cloud solution through the Orion SaaS platform, or as a custom solution tailored to specific organizational needs. The platform is designed to be accessible to both computational and medicinal chemists, enabling extreme-scale chemical space exploration with ease and without the need to enumerate intractable virtual libraries.