ROCS X - Prepare 3D Library
Description
This floe prepares a ROCS X 3D library for use in ROCS X 3D similarity searches. First, the floe reads in a 2D synthon library with reaction and reagent classifications. Then, it dedupes synthons within the reagent lists. Next, it generates 3D conformers for the deduped synthons and a sample of products using OMEGA. The product sample is obtained by pairing each synthon with a random synthon in its complementary reagent list.
Key Inputs and Outputs
The key input is a ROCS X 2D synthon library. This is typically output from the Reaction & Reagent Database - Multi-vendor - Parallel Export Synthon Collection Floe in the Generative Design Hit-to-Lead Floes package.
The key output is a ROCS X 3D library containing 3D conformers for the synthons and a product sample as well as duplicate information for the synthons. It is typically used as input for the ROCS X - Initialize 3D Search Floe.
Cost Considerations
The floe cost scales with the number of synthons in the input 2D synthon library. The computational bottleneck is typically caused by conformer generation for the product sample because products tend to be larger than synthons. For very large libraries, the computational bottleneck can be avoided by turning off product sampling (under Options: Sample Products, use Enable Sample Products: Off). This has implications when using the library in downstream floes (see the Speed Up Preparation of a Very Large ROCS X 3D Library How-To Guide in the documentation).
Promoted Parameters
Title in user interface (promoted name)
Inputs
ROCS X 2D Synthon Library (reagcoll): The input collection for the 2D synthon library.
Required
Type: collection_source
Reaction Constraint (rxnlist): Select one or more reactions from the sample reaction database list. Select ‘All’ to use all reactions and ‘Custom’ to use the Custom Reaction Constraint below.
Required
Type: string
Default: [‘All’]
Choices: [‘All’, ‘Custom’, ‘3-nitrile-pyridine’, ‘Buchwald-Hartwig’, ‘Buchwald_cross_coupling1’, ‘Buchwald_cross_coupling2’, ‘Ester_hydrolysis-amide_synthesis1’, ‘Ester_hydrolysis-amide_synthesis2’, ‘Grignard_alcohol’, ‘Grignard_carbonyl’, ‘Heck_non-terminal_vinyl’, ‘Heck_terminal_vinyl’, ‘Huisgen_disubst-alkyne’, ‘Mitsunobu_imide’, ‘Mitsunobu_phenol’, ‘Mitsunobu_sulfonamide’, ‘Mitsunobu_tetrazole_1’, ‘Mitsunobu_tetrazole_2’, ‘N-alkylation1’, ‘N-alkylation2’, ‘N-arylation_heterocycles’, ‘Negishi’, ‘Niementowski_quinazoline’, ‘O-alkylation’, ‘O-biarylation’, ‘Pictet-Spengler’, ‘Reductive_amination1’, ‘Reductive_amination2’, ‘Schotten-Baumann_amide’, ‘SnAr1’, ‘SnAr2’, ‘Sonogashira’, ‘Stille’, ‘Suzuki_cross_coupling’, ‘Wittig’, ‘benzimidazole_derivatives_aldehyde’, ‘benzimidazole_derivatives_carboxylic-acid/ester’, ‘benzofuran’, ‘benzothiazole’, ‘benzothiophene’, ‘benzoxazole_arom-aldehyde’, ‘benzoxazole_carboxylic-acid’, ‘decarboxylative_coupling’, ‘heteroaromatic_nuc_sub’, ‘imidazole’, ‘indole’, ‘nucl_sub_aromatic_ortho_nitro’, ‘nucl_sub_aromatic_para_nitro’, ‘oxadiazole’, ‘phthalazinone’, ‘piperidine_indole’, ‘pyrazole’, ‘spiro-chromanone’, ‘sulfon_amide’, ‘tetrazole_connect_regioisomere_1’, ‘tetrazole_connect_regioisomere_2’, ‘tetrazole_terminal’, ‘thiazole’, ‘triaryl-imidazole’, ‘urea’]
Custom Reaction Constraint (customrxnlist): Custom input for a comma-delimited list of reaction names to process from the reaction database. If Reaction Constraint is not ‘Custom’, this field will be ignored.
Type: string
Filter Ring Forming Reactions (filter_ringforming_flag): Toggle On to filter out ring-forming reactions. Off is not currently supported.
Type: boolean
Default: True
Choices: [True, False]
Use Deduped Reagents (if available) (use_deduped_reagents_flag):
Type: boolean
Default: False
Choices: [True, False]
Outputs
Temporary Collection (temporary_collection): This collection is created by the floe for internal use during the run and is automatically deleted by the floe when it finishes.
Type: collection_sink
Default: Temporary Collection
ROCS X 3D Library Collection (out_coll): The name of the output collection for the 3D library.
Required
Type: collection_sink
Default: ROCS X 3D Library
Synthon Failures Collection (synthon_failures_out): The name of the output collection for synthon prep failures.
Type: collection_sink
Default: ROCS X Prepare 3D Library Failures (Synthons)
Product Failures Collection (product_failures_out): The name of the output collection for product prep failures.
Type: collection_sink
Default: ROCS X Prepared 3D Library Failures (Products)
Options: Filtering
Max Molecular Weight (mw_max): Molecules with molecular weight greater than this value will be filtered out. If unspecified, this cube will not filter out molecules with high molecular weight.
Type: decimal
Default: 500
Min Molecular Weight (mw_min): Molecules with molecular weight less than this value will be filtered out. If unspecified, this cube will not filter out molecules with low molecular weight.
Type: decimal
Max Rotatable Bond Count (rot_bond_max): Molecules with rotatable bond count greater than this value will be filtered out. If unspecified, this cube will not filter out molecules with high rotatable bond count.
Type: integer
Default: 15
Min Rotatable Bond Count (rot_bond_min): Molecules with rotatable bond count less than this value will be filtered out. If unspecified, this cube will not filter out molecules with low rotatable bond count.
Type: integer
Max Count Undefined Atom Stereo (atom_stereo_max): Molecules with count undefined atom stereo greater than this value will be filtered out. If unspecified, this cube will not filter out molecules with high count undefined atom stereo.
Type: integer
Default: 3
Max Count Undefined Bond Stereo (bond_stereo_max): Molecules with count undefined bond stereo greater than this value will be filtered out. If unspecified, this cube will not filter out molecules with high count undefined bond stereo.
Type: integer
Default: 3
Options: Sample Products
Enable Generate Conformers (gen_confs_flag):
Type: boolean
Default: True
Choices: [True, False]
Enable Sample Products (sample_products_flag):
Type: boolean
Default: True
Choices: [True, False]
Product Normalization (protomer_prep_mode): Tautomer and ionization state normalization applied to products.
Type: string
Default: Get reasonable protomer and set neutral pH
Choices: [‘Get reasonable protomer and set neutral pH’, ‘Set neutral pH’, ‘None’]
Number of Synthon Pairs (num_rand_pairs): The number of random complementary components to pair with each synthon. The sampling method ensures all synthons are represented at least once. At the default value (1), the number of sampled products will be equal to the number of synthons. Warning: Increasing this from the default value (1) will significantly increase the cost of running the floe.
Type: integer
Default: 1
Pairing Attempts (while_max_count): The number of times to attempt synthon pairing when sampling products. If the number of attempts is exceeded, the synthon will be passed during product sampling.
Type: integer
Default: 10
Options: Advanced
Validate Conformers (validate_conformers_flag):
Type: boolean
Default: True
Choices: [True, False]
Read Synthon Chunk Size (read_reagent_chunk_size): The number of 2D synthons to process in a chunk.
Type: integer
Default: 10000
Product Chunk Size (product_chunk_size): The number of 2D unenumerated products to process in a chunk. The maximum value is 2000.
Type: integer
Default: 500
Synthon Chunk Size (synthon_chunk_size): The number of 2D enumerated synthons to process in a chunk.
Type: integer
Default: 5000
FastROCS Chunk Size (records_per_shard): The target number of records in a FastROCS shard. The recommended default is 800,000.
Type: integer
Default: 800000