I’m currently attempting to generate conformers of a set of small molecule “building blocks” (MW < 250 Da) that are tethered by a common substructure that they all share (for example a carboxylic acid). Essentially, this is a surrogate method for pairwise flexible alignments, where both molecules are aligned by their common carboxylic acid (for example), then the other atoms within one molecule are flexibly aligned onto the other atoms from the other molecule in a way to maximize overlap. Sampling many conformers of both molecules, then choosing the pair with the most 3D overlap via downstream nodes should achieve more or less the same goal, because the flexible alignment takes a very long time (though maybe this method will not be quite as good…that’s actually what I’m trying to investigate).The “Templated Conformer Generation” node from Vernalis sounds like a great tool to do this, based on its description.
I am running into some issues using this node, though.
- As other posts have mentioned, it tends to crash KNIME unless I partition my input into relatively small subsets. It seems like a workaround was found in the other forum posts because the poster could just use the “RDKit Add Conformers” node, but I don’t believe that node would help in my case because it doesn’t have the option to tether all molecules to a common substructure.
- I’ve tried a couple of different methods of setting the “template” to just a carboxylic acid ([OH]C=O)…both having it as a RDKit mol column in the input table, or defining a Mol flow variable. In either case, I receive the error below
Execute failed: (“KeyErrorException”): null
Turning the template off altogether or using the molecule column as template and template as molecule seems to execute fine, although it’s obviously not what I’m actually trying to do.
- Apologies in advance if there is a simple answer to this–I’m not a programmer by any means. But in the cases from 2. where I successfully got output from the node, the “Conformers” output column seems to be just a list of SMILES strings if “RDKit” is selected as the “Conformer output format”, or text from a Mol file if “Mol” is selected. How can I convert that text output into 3D structures that I could save as a .sdf, or view in a 3D structure viewer etc? Molecule Type Cast doesn’t seem to recognize them as molecules.
Here is an example workflow: