RIDE

RIDE (Rapid Isostere Discovery Engine) is a fast 3D molecular similarity search tool developed by Molsoft L.L.C. Built on Atomic Property Fields (APF), RIDE searches databases of compound conformers to identify molecules that are isosteric to a query compound — meaning they share similar 3D configurations and distributions of atomic properties. RIDE is available as part of the ICM-Pro + VLS package and is designed for medicinal chemists and computational scientists working in drug discovery.

Powered by a GPU-based implementation, RIDE is capable of processing approximately 1.5 million conformers per second on a single GPU card, enabling 3D virtual screens of millions of compounds with a level of interactivity comparable to traditional 2D searches. Benchmarking on the DUDe dataset demonstrates that RIDE produces enrichment results on par with much slower standard flexible APF virtual library screening methods.

Pre-Prepared Conformer Libraries

• Enamine REAL database
• NIH Synthetically Available Virtual Inventory (SAVI)
• WuXI Galaxi database

Users can also screen any giga-sized library within the ICM environment beyond these pre-prepared options.

Key Applications

• Virtual screening — efficiently screen giga-sized compound libraries to identify active candidates.
• Scaffold hopping — discover structurally novel chemicals based on a known lead compound.
• Hit follow-up — rapidly identify new chemicals with similar 3D pharmacophoric binding properties to a lead.
• Core replacement — perform core replacement directly within the ICM 3D ligand editor.

Query Fine-Tuning Capabilities

• Atom Weighting — contributions of different portions of the molecule can be modulated using per-atom weights, allowing users to reflect the relative importance of specific chemical moieties in the search.
• Excluded Volumes with Shape Matching — an envelope penalty can be applied to regions surrounding all or part of the query molecule, prioritizing hits that lack bulky extensions in constrained binding regions.

RIDE provides both a simple web-based interface for ease of use by chemists and a batch scripting option for automated or high-throughput workflows, making it accessible across a range of user expertise levels and computational environments.