ChemoDOTS

ChemoDOTS generates synthesizable chemical libraries around an activated hit compound to support hit-to-lead optimization in drug discovery.

Key Features:

• Automated Reaction Detection and Selection: Automatically identifies reactive functions in the hit molecule and proposes compatible chemical transformations using an extensive library of encoded reactions commonly used in pharmaceutical hit-to-lead optimization.
• Library Generation: Couples compatible chemical building blocks to the hit scaffold to generate a raw chemical library of derivatized compounds.
• Post-Processing Filters: Applies filters to extract subsets of compounds with specified physicochemical properties.
• Stereoisomer and Tautomer Computation: Enumerates explicit stereoisomers and tautomers for each library molecule.
• 3D Conformer Generation: Generates a 3D conformer for each compound to enable integration with docking software in virtual screening workflows.

Scientific Applications:

• Hit-to-Lead Optimization: Explores chemical space around an initial hit to propose synthetically tractable lead series.
• Virtual Screening and Lead Identification: Produces libraries compatible with docking workflows to support virtual screening and prioritization of lead candidates.
• Physicochemical Property-Driven Design: Enables selection of compound subsets tuned to target physicochemical criteria for downstream testing.

Methodology:

Input an activated hit molecule; automated detection of reactive functions; suggestion of chemical transformations from a curated set of encoded reactions; user selection of reactions; coupling of compatible building blocks to form a raw library; application of post-processing filters; enumeration of stereoisomers and tautomers; and generation of 3D conformers.