LEAD DISCOVERY

FastROCS

GPU-accelerated Shape Similarity Search

Scale your virtual screening and lead hopping to billions and beyond with FastROCS^TM.

Get near-instantaneous results for your virtual screening and lead hopping needs. FastROCS performs 3D alignment and scoring, based on a robust Gaussian-based description of shape and chemical features, at speeds approaching those of 2D methods. FastROCS Plus integrates 3D ligand- and structure-based screening into a streamlined, automated workflow. This unparalleled speed of FastROCS allows you to conduct highly accurate 3D shape and chemical feature similarity calculations on millions of molecules within seconds, delivering hits that are highly structurally diverse compared to those from 2D searches.

Our prospective study describes how conceptually simple shape-matching approaches can identify potent and selective compounds by searching ultralarge virtual libraries, demonstrating the applicability of such workflows and their importance in early drug discovery. -- Petrovic et al. (JCIM, 2022)

FastROCS: Unparalleled Speed in 3D Shape and Chemical Feature Similarity Searching.

Features

Get near-instantaneous results. Processes millions to hundreds of millions of conformations per second
Launch jobs and view results using VIDA desktop visualizer or Orion web interface
Accepts pocket queries and shape queries, plus mixed queries combining molecule, shape, and pocket inputs, so you can screen with ligand and/or structural information
Overlay results are intuitive and visually informative
Support both Gaussian and grid-based shape query
FastROCS Plus. Seamlessly combine ligand- and structure-based approaches in one step

FastROCS Plus: Seamlessly combine 3D ligand- and structure-based screening

FastROCS_Plus_Ligand_Structure_Based_Screening_image

FastROCS™ Plus offers a comprehensive, turnkey solution that integrates 3D ligand- and structure-based screening into a streamlined, automated workflow

FastROCS Plus provides scientists with a high-performance, GPU-accelerated shape-based screening tool designed for rapid, large-scale molecular comparison. Built on the proven ROCS® technology, FastROCS Plus leverages parallel GPU processing to deliver ultra-fast shape and chemical feature similarity calculations across millions of compounds in seconds. Researchers can screen from one to hundreds of shape or molecule queries at once, with results consolidated into a single ranked hit list based on each molecule's best match across all queries. For added confidence, top hits can optionally be re-scored using ROCS, docking, or a consensus of both, with Pareto ranking available when a target structure is known.

Ideal for virtual screening campaigns and early-stage drug discovery, FastROCS Plus enables researchers to explore chemical space more efficiently, prioritize candidates faster, and make data-driven decisions with confidence. Combining speed, scalability, and precision, FastROCS Plus delivers better hits, because better hits start with better screening.

How Scientists are Using FastROCS

FrankenROCS, a novel shape-based virtual screening pipeline, was developed by teams at UCSF and Relay Therapeutics to address limitations in lead optimization, particularly for SARS-CoV-2 macrodomain inhibitors with poor membrane permeability. This pipeline integrates OpenEye's FastROCS for 3D similarity searching with an active learning algorithm (Thompson sampling).

This methodology enabled the efficient exploration of the 22-billion-molecule Enamine REAL database, overcoming the prohibitive scale of traditional screening. The approach successfully identified submicromolar inhibitors with improved cell permeability and metabolic stability, achieving significant potency gains through fragment linking. This demonstrates a scalable strategy for discovering structurally validated, drug-like candidates from synthesis-on-demand libraries. Link to publication.

"ROCS and its graphics processing unit implementation FastROCS are in- dustry standards that have been applied in many published and unpublished inhibitor discovery efforts over the past 20 years." -- Correy et al. (Sci. Adv., 2025)

Acceleration of shape searching on the GPU and on Cloud. Boehringer-Ingelheim (BI) successful hit finding search of 1 billion compounds using ROCS took 11 CPU years (or 2 days on 2000 CPU cluster). Today, searching 1 billion compounds on FastROCS takes less than 1 day (4 GPU cluster) or less than 30 minutes on AWS Cloud.

FAQs

: FastROCS can be accessed both in its toolkit form (FastROCS TK) and on OpenEye's Orion Modeling Platform.
: ROCS^® is a comprehensive tool for fast shape and chemical feature similarity, able to process hundreds of molecules per CPU second.

FastROCS combines the state-of-the-art science from ROCS with the speed of the GPU. With FastROCS, you can search virtual libraries of billions of compounds or cluster millions of molecules by shape.

FastROCS Plus extends the search capabilities of FastROCS by using consensus scoring with high-speed docking. FastROCS Plus seamlessly combines ligand- and structure-based approaches in one step.

FastROCS and FastROCS Plus - trusted science, extreme speed, and unlimited scale! Find your next drug candidate, faster.
: FastROCS TK supports both Gaussian and grid-based shape queries, expanding the types of queries inputs to include active site negative images, composite queries combining grids and molecules, and queries derived from crystallographic density.

Modeling

The Modeling suite of toolkits provides the core functionality underlying OpenEye's defining principle that shape & electrostatics are the two fundamental descriptors determining intermolecular interactions. Many of the toolkits in the Modeling suite are directly associated with specific OpenEye applications and can, therefore, be used to create new or extend existing functionality associated with those applications.

OEChem TK OEChem TK Core chemistry, advanced peptide handling, and high-performance molecule file I/O
FastROCS™ TK Real-time shape similarity for virtual screening, lead hopping & shape clustering
OEDocking TK Molecular docking and scoring
Omega TK Conformer generation
Shape TK 3D shape description, optimization, and overlap
SiteHopper TK Rapid comparison of protein binding sites
Spicoli TK Surface generation, manipulation, and interrogation
Spruce TK Protein preparation and modeling
Szybki TK Force field based focused optimization and entropy estimations
OEFF TK Force fields and general optimization tools
Szmap TK Understanding water interactions in a binding site
Zap TK Calculate Poisson-Boltzmann electrostatic potentials
Bioisostere TK 3D fragment similarity, lead optimization, and analog generation
Eon TK Molecular shape and electrostatic overlap

Cheminformatics

The Cheminformatics suite of toolkits provides the core foundation upon which all the OpenEye applications and remaining toolkits are built.

OEChem TK OEChem TK Core chemistry, advanced peptide handling, and high-performance molecule file I/O
OEDepict TK 2D Molecule rendering and depiction
Grapheme™ TK Advanced molecule rendering and report generation
GraphSim TK 2D molecular similarity (e.g. fingerprints)
Lexichem™ TK Name-to-structure, structure-to-name, foreign language translation
MolProp TK Molecular property calculation and filtering
Quacpac TK Tautomer enumeration and charge assignment
OEMedChem TK Matched molecular pair analysis, fragmentation utilities, and molecular complexity metrics
Saiph TK: Extracting, transforming, and loading (ETL) files and records