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 Bonds	Conformers
< 8	50
8 - 12	200
> 12	300

When a template is supplied, then the number of rotatable bonds used in this calculation is adjusted to account for the rigid template.

Templates

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