Templated Conformer Generation (RDKit)

This node generates conformers for input molecules using parallel processing, outputting all the generated conformers for each input row as a set of List Cells appended to the input row. Conformers arec returned in ascending energy order, and optional filters for maximum relative energy (kcal/mol) may be added, along with a minimum RMSD filter, which removes 'similar' conformers.

There are options to use the 'basic knowledge' and 'experimental torsions' knowledge-based conformer generation refinements of Riniker and Landrum ('Better Informed Distance Geometry: Using What We Know To Improve Conformation Generation', J. Chem. Inf. Model., 2015, 55, 2562-2574; DOI: 10.1021/acs.jcim.5b)

Number of Conformers

The number of conformers generated can optionally be determined from the number of rotatable bonds according to the parameters in 'Freely Available Conformer Generation Methods: How Good Are They?' (J. Chem. Inf. Model., 2012, 52, 1146-1158; DOI:10.1021/ci2004658)

The values used are:

Rotatable BondsConformers
< 850
8 - 12200
> 12300
When a template is supplied, then the number of rotatable bonds used in this calculation is adjusted to account for the rigid template.


Optionally, a template molecule may be supplied. This can be supplied on a row-by-row basis from a second input column, or as a Mol block pasted into the node settings (or supplied from a flow variable). In either case, the following process is applied to the template supplied in order to use it as the basis of a template for conformer generation:

  1. If the template is a substructure of the molecule, then it is used as such - where there are multiple possibilities for matching the template to the molecule, the first is used arbitrarily
  2. Otherwise, a Maximum Common Substructure (MCS) is generated between the template and the molecule. Currently, this requires atoms to match (otherwise H/non-H matches cause problems for conformer generation). NB: In a future update, this will allow matches between differing heavy atoms as an additional option.

The template can be applied with or without tethers. Tethers add extra points to the forcefield in the positions of the template atoms, and distance constraints from these points to the matched atoms, effectively aligning the generated conformers closely to the actual template orientation. If tethers are not used, simple distance constraints between all pairs of atoms matching the template atoms are added to match the corresponding distances in the template. The conformer will thus not be exactly aligned to the template, although it should be geometrically constrained to be a rotation/translation.

Finally, an RMSD filter may be applied to limit the RMSD deviation of the conformers from the template (this maximum RMSD filter should not be confused with the minimum RMSD filter between conformers mentioned above)

Geometry Optimisation

Following conformer generation, the conformers undergo geometry optimisation using one of 3 forcefields (UFF, MMFF94, MMFF94S). Optionally, if the forcefield is not parameterised fully for the molecule, the node can default to use the UFF forcefield, which paramaterises most 'organic' molecules. If the UFF forcefield is substituted, a message is sent to the console log. Molecules for which no optimisation was possible have missing values in the conformer energy column. It should be noted that the conformer energy will include any terms for constraining to a template, and explicit Hydrogen contributions.

This node was developed by Vernalis Research. For feedback and more information, please contact knime@vernalis.com


Molecule column
The input molecule column column
Ensure H's added
Hydrogens are added to incoming molecules prior to conformer generation
Use Rotatable Bond Count to Determine Number of Conformers
If set, then the number of conformers generated is based on the number of rotatable bonds in the input molecule (see above)
Number of conformers
The number of conformers to generate (The actual number returned maybe less than this depending on subsequent filtering options)
Max. Number of tries to generate conformer
The number of attempts to generate a conformer
Use experimental torsions
Should the experimental torsions be used
Use 'basic knowledge' - i.e. flat rings etc
Should 'basic knowledge' be used (i.e. flat rings etc)
Filter conformers by RMSD
Should conformers be filtered such that no two conformers are within the RMSD threshold of each other?
Minimum RMSD
The minimum allowed RMSD between conformers
Ignore H's
Should H's be ignored when calculating RMSD (faster!)
Remove H's
Should explicit H's be removed from the output molecules?
Conformer output format
The cell type to output (RDKit or Mol)

Template options

Output Actual Template for Row
The actual template used for the row, after any MCS calculation is added to the output table
Filter by Template RMSD
Should conformers be filtered according to their RMSD deviation from the template
Max template RMSD
The maximum permitted RMSD deviation from the template
Allow heavy atom mismatches
Allow template heavy atoms to match different heavy atoms in the molecule, e.g. morpholine / piperazine
Allow bond order mismatches
Allow template bond orders to match different bond orders in the molecule. Warning - this may prevent conformers from minimising
Match Valences
Require template atom valences to match
Match chiral tags
Require template atom chirality to match
Ring matches Ring Only
Require template atoms in rings to only match molecule atoms in rings
Match Complete Rings Only
Require matching of complete rings between template and molecule
Use tethers
Should tethers be used when aligning the conformer to the template? See above for details
Template Column
A column containing the templates
Template MOL Block
The Mol block of the template used for the entire table. If a template is supplied this way, then the actual template after MCS may be different for each row

Geometry Optimisation

The force field to use for geometry optimisation
Use UFF force field if unable to generate MMFF?
Fall back to the UFF if unable to paramaterise selected force field (see above for details)
The number of iterations to attempt convergence. Conformers which do not converge will be rejected. A value of 0 results in no geometry optimisation being attempted.
Filter by energy
Should the conformers be filtered by relative energy?
Max relative energy
The maximum relative energy for retained conformations

Flow Variables

Random Seed
Hidden setting only available via flow variables to fix the random seed used for conformer generation for testing purposes. The default value of -1 gives random behaviour

Input Ports

Table of input molecules and optionally templates for conformer generation

Output Ports

The generated conformers


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