Focused Library - Molecule Input

Category Paths

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

  • Solution-based/Hit to Lead/Generative Design/Reaction-based Libraries

  • Task-based/Library Prep & Design/Reaction-based Enumeration

  • Task-based/Virtual Screening - Structure-Based

  • Role-based/Medicinal Chemist

Description

This floe uses weighted ensemble molecular dynamics to sample the conformational dynamics of a target protein. Sampling is enhanced along a given set of normal modes (Tutorial: how to select normal modes as progress coordinates ). Note that the job can cost a few thousand dollars if the number of iterations for the simulation is too high (>500).

Promoted Parameters

Title in user interface (promoted name)

Inputs

Lead Molecule Dataset (lead_molecule): A dataset containing the lead molecule(s) to be transformed by reactions from the Reaction & Reagent Database. This dataset is assumed to be a dataset of ONE lead molecule due to the amplification of product(s) from the floe, but the input limit can be altered in the Advanced Focused Library Options tab. Generally small input datasets are expected.

  • Required

  • Type: data_source

Reaction & Reagent Database (rxndb): The name of the Reaction & Reagent Database to use.

  • Required

  • Type: file_in

Outputs

Output Dataset (output): Output dataset containing generated products.

  • Required

  • Type: dataset_out

  • Default: Reaction_products

Output Data (outdata): If OFF, just counts records, but does not output them.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

General Failures (failures): Output dataset containing input failures and reagents that failed to react.

  • Required

  • Type: dataset_out

  • Default: Input_failures

Output Failures (outfails): If OFF, just counts records, but does not output them.

  • Required

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Specific Product Failures (prodfailures): Output dataset containing specific reagent combinations that failed to react.

  • Required

  • Type: dataset_out

  • Default: Product_failures

Output Specific Failures (outprodfails): If OFF, just counts records, but does not output them.

  • Required

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Focused Library Options

Reactions or Reagents (queryclass): A list of reactions and/or reagents for selection of transforms. If this is a list of reagents, the input molecules will be verified against this reagent type or presumed to be this reagent type if the Verify Classifications switch is OFF.

  • Type: string

  • Default: []

  • Choices: [‘3-nitrile-pyridine’, ‘3-nitrile-pyridine:Diones_2_4’, ‘Buchwald-Hartwig’, ‘Buchwald-Hartwig:Amines’, ‘Buchwald-Hartwig:Halides_aryl’, ‘Buchwald_cross_coupling1’, ‘Buchwald_cross_coupling1:Amines’, ‘Buchwald_cross_coupling1:Aryl_halides’, ‘Buchwald_cross_coupling2’, ‘Buchwald_cross_coupling2:Amines’, ‘Buchwald_cross_coupling2:Aryl_halides’, ‘Ester_hydrolysis-amide_synthesis1’, ‘Ester_hydrolysis-amide_synthesis1:Amines’, ‘Ester_hydrolysis-amide_synthesis1:Esters’, ‘Ester_hydrolysis-amide_synthesis2’, ‘Ester_hydrolysis-amide_synthesis2:Amines’, ‘Ester_hydrolysis-amide_synthesis2:Esters’, ‘Grignard_alcohol’, ‘Grignard_alcohol:Halides_alkyl’, ‘Grignard_alcohol:Ketones_aldehydes’, ‘Grignard_carbonyl’, ‘Grignard_carbonyl:Halides_alkyl_aryl’, ‘Grignard_carbonyl:Nitriles’, ‘Heck_non-terminal_vinyl’, ‘Heck_non-terminal_vinyl:Halide_vinyl_aryls’, ‘Heck_non-terminal_vinyl:Non_terminal_vinyls’, ‘Heck_terminal_vinyl’, ‘Heck_terminal_vinyl:Halide_vinyl_aryls’, ‘Heck_terminal_vinyl:Terminal_vinyls’, ‘Huisgen_disubst-alkyne’, ‘Huisgen_disubst-alkyne:Alkyl_halides_alcohols’, ‘Huisgen_disubst-alkyne:Alkynes_disubstituted’, ‘Mitsunobu_imide’, ‘Mitsunobu_imide:Acetylacetamides’, ‘Mitsunobu_imide:Alcohols_primary_secondary’, ‘Mitsunobu_phenol’, ‘Mitsunobu_phenol:Alcohols_primary_secondary’, ‘Mitsunobu_phenol:Phenols’, ‘Mitsunobu_sulfonamide’, ‘Mitsunobu_sulfonamide:Alcohols_primary_secondary’, ‘Mitsunobu_sulfonamide:Sulfonamides’, ‘Mitsunobu_tetrazole_1’, ‘Mitsunobu_tetrazole_1:Alcohols_primary_secondary’, ‘Mitsunobu_tetrazole_1:Tetrazoles’, ‘Mitsunobu_tetrazole_2’, ‘Mitsunobu_tetrazole_2:Alcohols_primary_secondary’, ‘Mitsunobu_tetrazole_2:Tetrazoles’, ‘N-alkylation1’, ‘N-alkylation1:Amines’, ‘N-alkylation1:Benzyl_halides’, ‘N-alkylation2’, ‘N-alkylation2:Amines’, ‘N-alkylation2:Benzyl_halides’, ‘N-arylation_heterocycles_1’, ‘N-arylation_heterocycles_1:Boronic_acids_aryl’, ‘N-arylation_heterocycles_1:Pyrrole_like_nitrogens’, ‘N-arylation_heterocycles_2’, ‘N-arylation_heterocycles_2:Boronic_acids_aryl’, ‘N-arylation_heterocycles_2:Pyrrole_like_nitrogens’, ‘Negishi’, ‘Negishi:Alkyl_halides_primary1’, ‘Negishi:Alkyl_halides_primary2’, ‘Niementowski_quinazoline’, ‘Niementowski_quinazoline:Amides_primary’, ‘Niementowski_quinazoline:Aminobenzoic_acids’, ‘O-alkylation’, ‘O-alkylation:Benzyl_halides’, ‘O-alkylation:Phenols’, ‘O-biarylation’, ‘O-biarylation:Aryl_bromides’, ‘O-biarylation:Phenols’, ‘Pictet-Spengler’, ‘Pictet-Spengler:Aldehydes’, ‘Pictet-Spengler:Beta_amino_benzenes’, ‘Reductive_amination1’, ‘Reductive_amination1:Aldehydes’, ‘Reductive_amination1:Amines’, ‘Reductive_amination2’, ‘Reductive_amination2:Aldehydes’, ‘Reductive_amination2:Amines’, ‘Schotten-Baumann_amide’, ‘Schotten-Baumann_amide:Amines’, ‘Schotten-Baumann_amide:Carboxylic_acids’, ‘SnAr1’, ‘SnAr1:Amines’, ‘SnAr1:Heterohalides’, ‘SnAr2’, ‘SnAr2:Amines’, ‘SnAr2:Heterohalides’, ‘Sonogashira’, ‘Sonogashira:Alkynes’, ‘Sonogashira:Bromo_iodo_vinyls_aryls’, ‘Stille’, ‘Stille:Bromo_iodo_vinyls_aryls’, ‘Stille:Halides_aryl’, ‘Suzuki_cross_coupling’, ‘Suzuki_cross_coupling:Aryl_bromides’, ‘Suzuki_cross_coupling:Suzuki_boronics’, ‘Wittig’, ‘Wittig:Alkyl_halides_primary’, ‘Wittig:Ketones_aldehydes’, ‘benzimidazole_derivatives_aldehyde’, ‘benzimidazole_derivatives_aldehyde:Aldehydes’, ‘benzimidazole_derivatives_aldehyde:Aro_6_diamines’, ‘benzimidazole_derivatives_carboxylic-acid/ester’, ‘benzimidazole_derivatives_carboxylic-acid/ester:Aro_6_diamines’, ‘benzimidazole_derivatives_carboxylic-acid/ester:Carboxylic_acids’, ‘benzofuran’, ‘benzofuran:Alkynes’, ‘benzofuran:Halophenols’, ‘benzothiazole’, ‘benzothiazole:Aldehydes’, ‘benzothiazole:Aro_6_thiamines’, ‘benzothiophene’, ‘benzothiophene:Alkynes’, ‘benzothiophene:Halomethiols’, ‘benzoxazole_arom-aldehyde’, ‘benzoxazole_arom-aldehyde:Aminophenols’, ‘benzoxazole_arom-aldehyde:Benzaldehydes’, ‘benzoxazole_carboxylic-acid’, ‘benzoxazole_carboxylic-acid:Aminophenols’, ‘benzoxazole_carboxylic-acid:Carboxylic_acids’, ‘decarboxylative_coupling’, ‘decarboxylative_coupling:Carbonyl_benzoic_acids’, ‘decarboxylative_coupling:Halides_aryl’, ‘heteroaromatic_nuc_sub’, ‘heteroaromatic_nuc_sub:Amines’, ‘heteroaromatic_nuc_sub:Halo_aryls_activated’, ‘imidazole’, ‘imidazole:Alpha_halo_ketones’, ‘imidazole:Aryl_amidines_guanidines’, ‘indole’, ‘indole:Alkynes’, ‘indole:Haloanilines’, ‘nucl_sub_aromatic_ortho_nitro’, ‘nucl_sub_aromatic_ortho_nitro:Amines’, ‘nucl_sub_aromatic_ortho_nitro:Ortho_nitro_halides’, ‘nucl_sub_aromatic_para_nitro’, ‘nucl_sub_aromatic_para_nitro:Amines’, ‘nucl_sub_aromatic_para_nitro:Para_nitro_halides’, ‘oxadiazole’, ‘oxadiazole:Carboxylic_acids’, ‘oxadiazole:Nitriles’, ‘phthalazinone’, ‘phthalazinone:Hydrazines’, ‘phthalazinone:Ketobenzoic_acids’, ‘piperidine_indole’, ‘piperidine_indole:Indoles’, ‘piperidine_indole:Piperidines’, ‘pyrazole’, ‘pyrazole:Diones_2_4’, ‘pyrazole:Hydrazines’, ‘spiro-chromanone’, ‘spiro-chromanone:Ketophenols’, ‘spiro-chromanone:Piperadone_ketones’, ‘sulfon_amide’, ‘sulfon_amide:Amines’, ‘sulfon_amide:Sulfonyl_chlorides’, ‘tetrazole_connect_regioisomere_1’, ‘tetrazole_connect_regioisomere_1:Alkyl_bromides’, ‘tetrazole_connect_regioisomere_1:Nitriles’, ‘tetrazole_connect_regioisomere_2’, ‘tetrazole_connect_regioisomere_2:Alkyl_bromides’, ‘tetrazole_connect_regioisomere_2:Nitriles’, ‘tetrazole_terminal’, ‘tetrazole_terminal:Nitriles’, ‘thiazole’, ‘thiazole:Alpha_halo_ketones’, ‘thiazole:Thioamides’, ‘triaryl-imidazole’, ‘triaryl-imidazole:Aro_ethane_diones’, ‘triaryl-imidazole:Aroaldehydes’, ‘urea’, ‘urea:Amines’, ‘urea:Isocyanates’]

Custom Reactions or Reagents (customqueryclass): A list of custom reactions and/or reagents for selection of transforms. If this is a list of reagents, the input molecules will be verified against this reagent type or presumed to be this reagent type if the Verify Classifications switch if OFF. Any specification here supersedes any selection specified by the Reactions or Reagents above.

  • Type: string

Reaction Applied (rxnid): Name of the string field to identify the reaction.

  • Type: string

  • Default: ReactionId

Output Mol Field (outmol): Output molecule field.

  • Type: field_parameter::mol

Annotate Mol (outmolsmi): Name of the string field for the input molecule SMILES or blank to suppress.

  • Type: string

  • Default: OriginalMol

Annotate Rxn (outrxnsmi): Name of the string field for the reaction SMILES or blank to suppress.

  • Type: string

  • Default: Reaction

Strict Valences (strictval): If On, only output products with valid valences.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Check Valences (checkval): How to handle valence issues for the generated products.

  • Required

  • Type: string

  • Default: ignore

  • Choices: [‘ignore’, ‘fix’, ‘reject’]

SMILES Dedupe (dedupesmi): If ON, performs a deduplication of the product SMILES.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

SMILES Dedupe Memory (dedupesmimem): Product deduplication may require significant memory resources, specify the desired amount in MB.

  • Type: decimal

  • Default: 10240

DB Listing (listing): Generate a directory listing of the input Reaction & Reagent Database.

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Focused Library Filtering Options

Filter Output (filtering): Enable molecule filtering of the generated products (see type specified by Mol Filter).

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Mol Filter (mol_filter_type): Type of molecule filter to apply to the generated analogs.

  • Type: string

  • Default: BlockBuster

  • Choices: [‘Lead’, ‘Drug’, ‘BlockBuster’, ‘BlockBuster+PAINS’, ‘PAINS’, ‘Custom’]

Custom Filter File (mol_filter_file): A custom filter file resource to load.

  • Type: file_in

Mol Filter Summary Report (filter_summary): If ON, will generate a summary report of the rules that filtered molecules.

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Focused Library Property Generation

Compute Molecule Properties (mol_props): Which molecule properties to calculate.

  • Type: string

  • Default: [‘HeavyAtoms’, ‘MedChemInterest’, ‘MolComplexity’, ‘MolWeight’, ‘TPSA’, ‘XLogP’]

  • Choices: [‘HeavyAtoms’, ‘MedChemInterest’, ‘MolComplexity’, ‘MolWeight’, ‘TPSA’, ‘XLogP’]

Reagent Processing Options

Maximum Reagents (maxreagents): Maximum number of reagents to process.

  • Type: integer

  • Default: 100

Allow Functional Group Conversions (funcgroups): If ON, allows functional group translations for reagents in the database.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Sample Reagents (samplereagents): Sample this percentage of the total reagent available, limited by the (optional) Maximum Reagents total.

  • Type: integer

Advanced Focused Library Options

Lead Molecule Minimum Records (rec_min): The minimum number of lead molecule records allowed (default:1). Input lead molecule datasets that do not meet this threshold will terminate the floe. Use 0 to suppress validation.

  • Type: integer

  • Default: 1

Lead Molecule Maximum Records (rec_max): The maximum number of lead molecule records allowed (default:1). Input lead molecule datasets that exceed this threshold will terminate the floe. Use 0 to suppress validation.

  • Type: integer

  • Default: 1

Deprotecting Group Definitions (queryfngroupdefs): Optional name of a file resource containing reaction definitions to provide the deprotecting group transformation(s) of interest. If unspecified, the transformations from the database will be used.

  • Type: file_in

Deprotecting Groups (queryfngroups): A selectable list of specific deprotecting transformations from Deprotecting Group Definitions or from the database to apply to the lead molecule(s). If Deprotecting Group Definitions is unspecified, the database transformations are assumed to provide the functional group and/or deprotecting group transforms.

  • Type: string

  • Default: []

  • Choices: [‘All’, ‘Acid_Reduction’, ‘Alcohol_FullOxidation’, ‘Alcohol_PartialOxidation’, ‘Aldehyde_Reduction’, ‘AlkylHalide2Alcohol’, ‘AlkylHalide2Azide’, ‘AlkylHalide2Thiol’, ‘Amide_Reduction’, ‘Aniline_Diazotization’, ‘ArylHalide_Amination’, ‘ArylHalide_Borylation’, ‘Azide2Amine’, ‘Diazo2Cyano’, ‘Diazo2Halide’, ‘Diazo2Phenol’, ‘Ester_FullReduction’, ‘Ester_Hydrolysis’, ‘Ester_PartialReduction’, ‘Nitrile2Amide’, ‘Nitrile_Hydrolysis’, ‘Nitro_Reduction’]

Custom Deprotecting Groups (customqueryfngroups): A blank-delimited list of specific deprotecting transformations from Deprotecting Group Definitions or from the database to apply to the lead molecule(s). If Deprotecting Group Definitions is unspecified, the database transformations are assumed to provide the functional group and/or deprotecting group transforms. This specification always supersedes any list selections from Deprotecting Groups.

  • Type: string

Verify Classifications (verifyclass): If ON, each input molecule will be classified as to its reagent type and verified against the requested list of reactions or reagents. If OFF, and the requested list of reactions or reagents is not empty, the specified reagent types will be assumed without verification.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Classifier Memory Limit (classifiermem): The memory limit for the reaction classifier. It may need to be increased for large R&R Databases.

  • Required

  • Type: decimal

  • Default: 10240

Strict Classification (strictfeatures): If ON, all allowed and disallowed chemistry features are validated for classification of the input structures. If OFF, only required features are considered for reagent classifications.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Molecule ID Field (molid): Name of the string field for the molecule ID.

  • Type: field_parameter::string

Molecule SMILES Field (molsmi): Name of the string field for the molecule SMILES.

  • Type: field_parameter::string

Retain Input Dataset Fields (keepfields): If ON, it copies the input data record. If OFF, it discards all but the structure (which will change) and sends it downstream for processing.

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Verbosity (verbosity): Sets the output logging verbosity.

  • Type: string

  • Default: warning

  • Choices: [‘info’, ‘warning’, ‘error’, ‘debug’, ‘ddebug’]