Brood Advanced

This cube performs Brood calculation for a single input query molecule,

within the context of the optional additional protein. This advanced cube provides additional selectivity options to control the calculation.s Brood searches a database of known molecular fragments in order to identify fragments that are similar to the query fragment. Fragments most similar to the query fragment are returned.

Calculation Parameters

  • AttachColor Field (attachcolor) type: boolean: When this parameter is set to True, each molecule in the hitlist is annotated with the color atoms used in calculation of the chemical similarity.
    Default: True
  • AttachFrag Field (attachfrag) type: boolean: This parameter allows the user to control the annotation of each hitlist molecule with the SMILES of the fragment replacement (which makes up a portion). In VIDA, this is displayed as a depiction in the spreadsheet associated with the row of the molecule.
    Default: True
  • AttachmentCutoff Field (attachmentcutoff) type: decimal: Minimum acceptable attachment point score cutoff. The cutoff is for the shape-overlap score of the beginning and ending atom of each attachment bond. The default was chosen empirically to assure all fragments in the hitlist would have sensible attachment geometries. This value does not affect runs when the linkonly parameter is set to True.
    Default: 0.78 , Max: 2.0
  • AttachmentScale Field (attachmentscale) type: decimal: This parameter determines the balance between the chemical color score and the attachment point scores. Higher values indicate more weighting for the attachment-point alignment. This parameter has complex effects, please use it with care.
    Default: 1.5 , Max: 100.0
  • BondOrder Field (bondorder) type: boolean: When this parameter is set to True, only fragments with the same attachment bond orders as the query fragment are allowed.
    Default: True
  • bumpradius Field (bumpradius) type: decimal: This parameter determines the minimum distance between ligand heavy atoms and protein heavy atoms in the final relaxed solution for there to be considered a clash. New analogs with atoms closer than this cutoff to the active-site protein are discarded from the hitlist. If a selectivity protein is being used, at least one clashing atom must be found in order for the hitlist ligand to be retained. Because the molecular model of the protein is rigid it may be advantageous to this cutoff may need to be shorter than in a system with a flexible protein model.
    Default: 2.25 , Max: 100.0
  • CheckBond Field (checkbond) type: boolean: If this parameter is set to True, BROOD will check all bonds formed between new fragments and the rest of the query molecule and eliminate fragments that form bond oechem.Types that are typically unstable. Rather than being discarded entirely, these hits will be written in the brood_1.removed.oeb.gz file by default.
    Default: True
  • CheckGeometry Field (checkgeometry) type: boolean: By default, regardless of the attachment score (used primarily to drive the optimization) the fit of a fragment at the attachment points is controlled by geometric constraints. These require that the two attachment vectors that will be jointed into a bond are overlapping and pointing in roughly opposite directions. In some cases, particularly when the required geometry is unusual or strained, it can be useful to turn off this constraint check.
    Default: True
  • CPUs (cpu_count) type: integer: The number of CPUs to run this cube with
    Default: 1 , Min: 1, Max: 128
  • Cube Metrics (cube_metrics) type: string: Set of metrics to be collected

    Choices: cpu, disk, memory, network
  • Fragment Database file (db_file_field) type: file_in:
  • Temporary Disk Space (MiB) (disk_space) type: decimal: The minimum amount of disk space in MiB (1048576 B) this cube requires. Due to overhead, request a couple hundred MiB more than required.
    Default: 5120.0 , Min: 128.0, Max: 8589934592
  • ET Field (et) type: boolean: This parameter determines whether or not the electrostatic Tanimoto similarity is calculated. If true, electrostatic similarity is calculated on all of the fragments that also have a good shape score.
    Default: False
  • FileChrg Field (filechrg) type: boolean: When this parameter is true, the partial charges for electrostatic Tanimoto calculations are taken from the input files. If this flag is false, or the input file does not contain partial charges, MMFF charges will be used. The partial charges on the database molecules are pregenerated.
    Default: False
  • Property Field (filter_property) type: boolean: This parameter indicates whether ANY of the molecular properties should be used to eliminate compounds from consideration. While these filters can be useful, if a user expects to see a particular fragment or analog and it does not appear in the hitlist, it will often have been eliminated by the property filters. The Report File will indicate which if any property filter affected each fragment. If set to False, all of the related flags below become irrelevant.
    Default: False
  • Forcefield Field (forcefield) type: string: Force-filed for final analog optimization. In all cases, the Sheffield solvation model will be included in the potential.
    Default: MMFF94S
    Choices: MMFF94, mmff94, MMFF94S, MMFF94s, mmff94s
  • FromCT Field (fromct) type: boolean: This parameter indicates that the 3D conformer of the query molecule should be generated from the molecular graph, independent of the conformer in the input file. If this flag is False, BROOD will attempt to read the query molecule as a 3D structure. If the input format is 2D in nature, BROOD will generate a 3D conformer for the query molecule regardless of this parameter (i.e. a user can specify the query without a 3D structure). Please note that the database file should always contain 3D structures.
    Default: False
  • GPUs (gpu_count) type: integer: The number of GPUs to run this cube with
    Default: 0 , Max: 16
  • HitlistProt Field (hitlistprot) type: boolean: By default, in cases where protein structures play an integral role in the fragment selection, the protein is normally part of the hitlist in order to enable convenient visualization of the hitlist molecules in the active site. For some visualization environments, proteins are not appropriate. This parameter allows the user to control whether the proteins appear in the hitlist.
    Default: False
  • Idea Field (idea) type: boolean: Determine if the hitlist will be organized according to a reduced graph hierarchy. This is quite useful for clustering similar analogs and thus allowing a user to quickly scan the different analog families and drill-down into the most interesting clusters without needing to examine hundreds of analogs
    Default: True
  • Instance Tags (instance_tags) type: string: Only run on machines with matching tags (comma separated)
    Default: “”
  • Instance Type (instance_type) type: string: The type of instance that this cube needs to be run on
  • LinkOnly Field (linkonly) type: boolean: If this parameter is set to True, then the shape and chemistry of the fragment are ignored and ONLY the attachment point geometry (and constraints) are used to identify similar fragments. This is similar to Bartlett’s Caveat algorithm, one of the first algorithms in this genre. This type of search can be useful when trying to bridge one or more fragments without any prior knowledge, such as when linking two fragments in fragment-based design.
    Default: False
  • Max Rotors (max_rotors) type: integer: Cutoff of rotatable bonds. The cube will skip molecules with rotors more than the cutoff.
    Default: 40 , Min: 1, Max: 9999
  • MaxHit Field (maxhit) type: integer: Size of hitlists (1-50000)
    Default: 1000 , Min: 1, Max: 50000
  • MaxLocalStrain Field (maxlocalstrain) type: decimal: Maximum local strain allowed to fit analog molecule on top of query.
    Default: 6.5 , Max: 1000.0
  • Memory (MiB) (memory_mb) type: decimal: The minimum amount of memory in MiBs (1048576 B) this cube requires. Due to overhead, request a couple hundred MiB more than required.
    Default: 1800 , Min: 256.0, Max: 8589934592
  • Metric Period (metric_period) type: decimal: How often to sample metrics, in seconds
    Default: 60
    Choices: 1, 5, 10, 30, 60, 120, 180, 240, 300, Min: 1, Max: 300
  • NeutralpH Field (neutralph) type: boolean: Control whether the final molecules are set to an ionization state suitable at pH=7.4. Because new bonds are formed in the process of generating analogs, functional groups sometimes need adjustment even if their state was properly normalized prior to fragmentation. This flag allows the user to turn off pKa normalization.
    Default: True
  • Thread limit per CPU (pids_per_cpu_limit) type: integer: The number of threads per CPU
    Default: 32
  • Quicklook Field (quicklook) type: boolean: This parameter allows a user to do a quick (~2 minute) BROOD search. BROOD is designed to identify as many interesting hits as soon as possible. Thus while a thorough search may take minutes to hours, useful preliminary results can be generated in one or two minutes with this option.
    Default: False
  • RangeOffset Field (rangeoffset) type: integer: By default, the range of fragment heavy atoms specified by the rangesize parameter is centered around the same number of heavy atoms as the original query fragment. Instead, the user can use this parameter to bias search toward smaller or larger fragments with positive or negative values passed to this parameter.
    Default: 0 , Min: -100, Max: 100
  • RangeSize Field (rangesize) type: integer: By default, only fragments with a number of heavy atoms +/- N from the fragment being replaced are considered. This parameter lets the user control this setting. It should not be necessary to change this value except in unusual circumstances. This parameter determines the range of heavy atoms around query fragment’s number of heavy atoms to examine.
    Default: 6 , Min: 3, Max: 100
  • RingOnly Field (ringonly) type: boolean: This parameter’s purpose is to allow the user to control the number of ring atoms in the selected fragments. It has to do with a count of the number of ring atoms in the shortest path between attachment points in a fragment. In cases with more than 2 attachment points, all shortest paths are calculated and the number of ring atoms is summed. By default, the flag is set to True and requires at least 2 ring atoms in the path. If the flag is set to False, no ring-atom filtering is done.
    Default: True
  • ShapeCutoff Field (shapecutoff) type: decimal: Indicate the minimum required shape Tanimoto score required for a fragment to appear in the color, elect or queryAnalog hitlists. This cutoff is useful for cases when few shape-similar fragments exist in the database being searched.
    Default: 0.6 , Max: 1.0
  • Shared Memory (MiB) (shared_memory_mb) type: decimal: The amount of shared memory to allow a container to address
    Default: 64
  • Spot policy (spot_policy) type: string: Control cube placement on spot market instances
    Default: Prohibited
    Choices: Allowed, Preferred, NotPreferred, Prohibited, Required
  • Tautomer Field (tautomer) type: boolean: Adjustment of tautomer states can be necessary after joining the new fragments with the static portions of the original molecule. This parameter allows the user to turn off this normalization.
    Default: False
  • Title Delimeter Field (title_delm) type: string: When this string parameter is set, the score of each fragment in the hitlist will be appended to the title of the molecule. The parameter passed as the value is the delimiter between the original title and the addendum.

Field parameters

  • AroRingCt Out Field (aroringct_out) type: Field Type: Int: Field to store aroringct info
    Default: AroRingCt
  • Attach Out Field (attach_out) type: Field Type: Float: Field to store attach info
    Default: attach
  • ClusterID Out Field (clusterid_out) type: Field Type: Int: Field to store clusterid info
    Default: ClusterID
  • Color Out Field (color_out) type: Field Type: Float: Field to store color info
    Default: color
  • Combo Out Field (combo_out) type: Field Type: Float: Field to store combo info
    Default: combo
  • Complexity Out Field (complexity_out) type: Field Type: Float: Field to store complexity info
    Default: Complexity
  • Egan Out Field (egan_out) type: Field Type: Int: Field to store egan info
    Default: Egan
  • Extended Log Field (ext_log_field) type: Field Type: StringVec: Message extended log field
    Default: Extended Log Field
  • Fragment Out Field (fragment_out) type: Field Type: String: Field to store fragment info
    Default: Fragment
  • Freq Out Field (freq_out) type: Field Type: Int: Field to store freq info
    Default: freq
  • fsp3C Out Field (fsp3c_out) type: Field Type: Float: Field to store fsp3c info
    Default: fsp3C
  • HvyAtoms Out Field (hvyatoms_out) type: Field Type: Int: Field to store hvyatoms info
    Default: HvyAtoms
  • Cpddb Field (in_cpddb_field) type: Field Type: Chem.Mol: Input field containing the cpddb database.
  • None (in_mol_field) type: Field Type: Chem.Mol:
  • None (in_protein_field) type: Field Type: Chem.Mol:
  • Input Protein Field (in_select_field) type: Field Type: Chem.Mol: Input field containing the select protein.
  • LipinskiAcc Out Field (lipinskiacc_out) type: Field Type: Int: Field to store lipinskiacc info
    Default: LipinskiAcc
  • LipinskiDon Out Field (lipinskidon_out) type: Field Type: Int: Field to store lipinskidon info
    Default: LipinskiDon
  • LipinskiFail Out Field (lipinskifail_out) type: Field Type: Int: Field to store lipinskifail info
    Default: LipinskiFail
  • LocalStrain Out Field (localstrain_out) type: Field Type: Float: Field to store localstrain info
    Default: Local Strain
  • Log Field (log_field) type: Field Type: String: The field to store messages to floe report
    Default: Log Field
  • MolTanimotoCombo Out Field (moltanimotocombo_out) type: Field Type: Float: Field to store moltanimotocombo info
    Default: Mol TanimotoCombo
  • MolWt Out Field (molwt_out) type: Field Type: Float: Field to store molwt info
    Default: Mol Wt
  • None (out_mol_field) type: Field Type: Chem.Mol: Output record field for Brood results.
  • p(active) Out Field (pactive_out) type: Field Type: String: Field to store pactive info
    Default: p(active)
  • p(F>10%) Out Field (pfgt10percent_out) type: Field Type: Float: Field to store pfgt10percent info
    Default: p(F>10%)
  • RingCt Out Field (ringct_out) type: Field Type: Int: Field to store ringct info
    Default: RingCt
  • RingRatio Out Field (ringratio_out) type: Field Type: Float: Field to store ringratio info
    Default: RingRatio
  • Rotors Out Field (rotors_out) type: Field Type: Int: Field to store rotors info
    Default: Rotors
  • Shape Out Field (shape_out) type: Field Type: Float: Field to store shape info
    Default: shape
  • SourceMolLabels Out Field (sourcemollab_out) type: Field Type: String: Field to store sourcemollab info
    Default: Sourcec Mol Labels
  • SourceMols Out Field (sourcemols_out) type: Field Type: String: Field to store sourcemols info
    Default: Source Mols
  • tPSA Out Field (tpsa_out) type: Field Type: Float: Field to store tpsa info
    Default: tPSA
  • Veber Out Field (veber_out) type: Field Type: Int: Field to store veber info
    Default: Veber
  • XLogP Out Field (xlogp_out) type: Field Type: Float: Field to store xlogp info
    Default: XLogP

Hardware Parameters

Machine hardware requirements
  • Memory (MiB) (memory_mb) type: decimal: The minimum amount of memory in MiBs (1048576 B) this cube requires. Due to overhead, request a couple hundred MiB more than required.
    Default: 1800 , Min: 256.0, Max: 8589934592
  • Shared Memory (MiB) (shared_memory_mb) type: decimal: The amount of shared memory to allow a container to address
    Default: 64
  • Thread limit per CPU (pids_per_cpu_limit) type: integer: The number of threads per CPU
    Default: 32
  • Temporary Disk Space (MiB) (disk_space) type: decimal: The minimum amount of disk space in MiB (1048576 B) this cube requires. Due to overhead, request a couple hundred MiB more than required.
    Default: 5120.0 , Min: 128.0, Max: 8589934592
  • GPUs (gpu_count) type: integer: The number of GPUs to run this cube with
    Default: 0 , Max: 16
  • CPUs (cpu_count) type: integer: The number of CPUs to run this cube with
    Default: 1 , Min: 1, Max: 128
  • Instance Type (instance_type) type: string: The type of instance that this cube needs to be run on
  • Spot policy (spot_policy) type: string: Control cube placement on spot market instances
    Default: Prohibited
    Choices: Allowed, Preferred, NotPreferred, Prohibited, Required
  • Instance Tags (instance_tags) type: string: Only run on machines with matching tags (comma separated)
    Default: “”

Metrics Parameters

Cube Metric Parameters
  • Metric Period (None) type: decimal: How often to sample metrics, in seconds
    Default: 60
    Choices: 1, 5, 10, 30, 60, 120, 180, 240, 300, Min: 1, Max: 300
  • Cube Metrics (None) type: string: Set of metrics to be collected

    Choices: cpu, disk, memory, network