Novel Hits From Beyond the Known

Search Trillions with ROCS X

ROCS X^TM is OpenEye’s next-generation virtual screening at the trillion-compound scale on the Orion^® Software-as-a-Service (SaaS) Molecular Design platform. Built to go beyond commercial catalogs, ROCS X constructs ultra-large 2D and 3D chemical libraries from reaction-informed synthons and intelligently explores them using active learning. Leveraging industry-leading tools for 3D conformation and shape-based search of OMEGA, ROCS^®, and FastROCS, OpenEye's ROCS X enables rapid identification of relevant, synthesizable molecules without the need to enumerate them all. Finding hits is now faster and smarter!

OpenEye's ROCS X substructure and 3D search based on query partitioning schedule in synthon space lets you unlock massive, synthesizable chemical space in the trillions to speed up your hit finding. Figure shows an example of query partitioning on N-[3-(fluoromethyl)phenyl]-4-methyl-3-(methylamino)benzamide.

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 beyond what's available in vendor databases.
Built for Practical Impact.
Jointly developed with an industry partner, ROCS X integrates cutting-edge 3D search and AI-guided sampling to deliver results that accelerate hit discovery beyond vendor catalogs.
Reaction-Aware Synthon Libraries.

ROCS X generates virtual compounds using known reactions and a curated reagent database. These molecules are easily synthesizable, and stored in a compact, unenumerated format.
Smart Sampling with AI.

ROCS X uses AI (Bayesian bandits) to efficiently explore product space. You can recover high-ranking hits by sampling fractions of the virtual library.
3D Shape-Based Search.

ROCS X leverages our best-in-class FastROCS and ROCS for accurate 3D similarity scoring using ligand or any shape queries. Align your search with biologically relevant shapes, even in the absence of known ligands.
Seamless Integration in Orion.

ROCS X is fully integrated into the Orion cloud platform, enabling scalable, on-demand virtual screening workflows from query to hitlist.

"Using Cadence ROCS X, scientists at Treeline can now search trillions of drug-like molecules—an achievement that was unimaginable just a few years ago... By running ROCS X, we've identified novel chemical matter leading to promising 3D ligand-protein structures across multiple drug discovery projects.” -Eric Manas, Senior Vice President of Medicine Design, Treeline Biosciences.

Hear from Our Customers

OpenEye, Cadence Molecular Sciences, ROCS X has already been applied in diverse discovery programs across therapeutic areas at Treeline Biosciences. To date:

150+ novel compounds sourced and synthesized
Multiple co-crystal structures confirmed
High synthetic success rate due to reaction-aware design
Enabled discovery of hits not found in any vendor catalog

View the press release here.

Larger Libraries, Faster Search, Synthesizable Hits

OpenEye’s Rapid Overlay of Chemical Structures (ROCS and FastROCS) provides a validated 3D shape similarity method that quantitatively correlates molecular similarity with the likelihood of comparable biological activity. The Tanimoto Combo (TC) score, which combines shape and atom-based features, is particularly effective in predicting biological similarity between molecules.

ROCS X integrates FastROCS (GPU version of ROCS) with a reaction-aware, synthon-based architecture to enable virtual screening of over one trillion synthetically accessible compounds. The library is built from ~7.4 million purchasable building blocks and curated chemical reactions.

ROCS X integrates industry-leading ROCS and FastROCS for 3D similarity searching. Using Bayesian bandits, this 3D ROCS X approach efficiently explores chemical space at the trillion-compound scale, yielding shape-similar hits in record time.

ROCS X efficiently identifies top-scoring, chemically relevant hits while sampling as little as 0.0002% of a 1.3-trillion-compound library at low computational cost, making it a scalable solution for modern drug discovery.

Novel Synthesizable Hits with Smart Sampling

To efficiently explore the vast 3D chemical space, ROCS X employs an AI-guided active learning approach. Our Bayesian bandits approach prioritizes sampling, while FastROCS evaluates shape similarity. Searches are guided by queries derived from ligands or any shape queries designed by scientists, enabling ROCS X to identify top hits with minimal sampling.

The Tanimoto Combo score (shape overlap + atom-based overlap) has been demonstrated in drug discovery applications as a superior method for quantitatively estimating the likelihood that two molecules will exhibit similar biological activity.

Evaluating the Tanimoto Combo score, ROCS X recovers over 95% of top hits while sampling as little as 0.0002% of a 1.3-trillion-compound library. This enables the identification of top-scoring, chemically relevant hits with high efficiency and low computational cost, making ROCS X a cost-effective and scalable solution for modern drug discovery.

How OpenEye 3D Search ROCS X can benefit you:

Search Beyond the Known
Go far beyond what’s commercially available. Discover novel chemical compounds that’s both relevant and synthesizable. Don't miss out on your best hits.
Speed Meets Scale 
Screen trillions in hours. Reduce compute and storage by orders of magnitude with smart, unenumerated searching.
Built for Scientists
Easy to use. Designed for computational and medicinal chemists to search extreme chemical space with ease.

Want to see ROCS X in action or explore how it fits into your discovery pipeline? Contact us to schedule a demo or discuss your specific screening goals.

Search trillions. Find what others miss, beyond purchaseable compound space. Unlock massive, synthesizable chemical space via substructure and 3D search with physics and AI methods built for modern discovery teams.

Search More, Spend Less, Find Hits: Trillions at the Cost of Millions

FAQs

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.
Reducing computational cost is important.

Use FastROCS when...

You have complete molecular structures for all compounds.
You need to perform an exhaustive search of every molecule in the database.
Your database size allows full molecular enumeration.

In short, ROCS X is best for exploring ultra-large, reaction-based virtual libraries at low cost, while FastROCS is ideal for exhaustive 3D searches on fully enumerated, smaller-scale (millions to billions) molecular databases.

Building blocks from vendors such as Enamine, Molport, and Mcule, together with more than forty commonly used reactions, are available to users. This combination enables access to a virtual library of over 1.3 trillion synthesizable compounds.

Users may also choose add-ons that allow incorporation of in-house reagents and reactions into the existing library. For details, please contact sales@eyesopen.com.

Compounds can be ordered by submitting a quote request directly to the vendor. Please include the following information in your request:

Requested structures (in SMILES or SD format)
Quantity required

Vendor contact details:

Mcule: order@mcule.com
Enamine: libraries@enamine.net
Molport: customerservice@molport.com

ROCS X is designed to explore chemical space beyond the reach of existing methods. Customers have used OpenEye’s ROCS X to search libraries containing hundreds of trillions of virtual molecules.

ROCS X is available as an off-the-shelf cloud solution or as a custom solution to precisely match your company's business needs.

Please contact us at sales@eyesopen.com