BROOD - 3D Fragment Replacement

Category Paths

Follow one of these paths in the Orion user interface, to find the floe.

  • Product-based/BROOD

  • Role-based/Computational Chemist

  • Solution-based/Virtual-screening/DB Search

  • Task-based/Scaffold-Hopping

  • Role-based/Medicinal Chemist

Description

BROOD - 3D Fragment Replacement is a lead generation tool designed to generate new and diverse compounds that satisfy isosteric and chemical feature constraints while also incorporating synthetic feasibility. Starting with a hit or lead molecule, BROOD generates bioisosteric analogs by replacing user-specified portions of the lead with fragments that have similar shape and electrostatics, but with potentially novel connectivity and chemistry. Fragments and scaffold couplings are derived within the scope of a known chemical space, based on the specified Brood Fragments Database.

The default Brood Fragments Database Collection named ‘brood-database-chembl-xxx’ is available in organizational data, where xxx is a version number.

Promoted Parameters

Title in user interface (promoted name)

Input parameters

Brood Database (collection): Brood database collection

  • Required

  • Type: collection_source

Brood Query (in_query): (Optional) Dataset containing Brood Query

  • Type: data_source

Query Sketcher (ui_result): (Optional) Dataset containing 3D molecule

  • Type: fragment_input

Design Unit (in_du): (Optional with sketcher) Dataset containing design unit

  • Type: data_source

Components to keep as the ‘protein’ (protein_mask): DU components to use as the ‘protein’.

  • Type: string

  • Default: [‘protein’, ‘nucleic’, ‘cofactors’, ‘other_ligands’, ‘other_cofactors’]

  • Choices: [‘protein’, ‘nucleic’, ‘ligand’, ‘solvent’, ‘metals’, ‘counter_ions’, ‘lipids’, ‘packing_residues’, ‘sugars’, ‘undefined’, ‘cofactors’, ‘excipients’, ‘polymers’, ‘post_translational’, ‘other_proteins’, ‘other_nucleics’, ‘other_ligands’, ‘other_cofactors’]

Output parameters

Save Query (save_query): Save query built using Sketcher

  • Required

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Query output (data_out): Output for BROOD - 3D query

  • Required

  • Type: dataset_out

  • Default: Output - brood query

Output Dataset (out): Output dataset of successful calculations

  • Required

  • Type: dataset_out

  • Default: Output for BROOD - 3D Fragment Replacement

Failed Dataset (failed): Output dataset of failed calculations.

  • Required

  • Type: dataset_out

  • Default: Failed Output for BROOD - 3D Fragment Replacement

Brood settings

Generate Brood clusters report (create_report): Whether or not to generate Brood clusters report

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Score Type (score_type): Score type to be used for Overlay

  • Type: string

  • Default: rocs

  • Choices: [‘rocs’, ‘ET’, ‘LinkOnly’]