I am building a script to compare shapes of Rdkit generated conformers for a query ligand to a reference ligand extracted from a template protein-ligand complex. For this I want to use the shape similarity Tanimoto metric ShapeTanimotoDist() provided by Rdkit. It seems however that this function does not pre-align the molecules when computing shape similarity. When I did some searches I stumbled upon this discussion 10 years ago wherein someone attempted something similar: https://sourceforge.net/p/rdkit/mailman/message/21906484/.
Quoting Greg Landrum:
There is no alignment step. If you want reasonable shape comparisons, you first need a reasonable alignment of the molecules. The RDKit doesn't currently provide a practical method of doing this alignment.
So I am wondering if since then this issue has been resolved and that it therefore would be reasonable to just use this function in a standalone fashion to compare shapes of molecules? In the documentation it states under ShapeTanimotoDist() that it uses a "predefined alignment", which is not elaborated further. I have looked into documentation for the 2 molecule aligning functions Rdkit provides: AlignMol and Open3DAlign (O3A) https://www.rdkit.org/docs/source/rdkit.Chem.rdMolAlign.html. For some reason AlignMol does not work for me (Runtime error), albeit O3A which is supported in Rdkit since 2014 did allow me to compare the conformers with ref ligands. However, when creating an O3A object, is there a way to somehow retrieve the coordinates of the conformer and ref molecule alignment to feed into ShapeTanimotoDist()? And also perhaps visualize this using PyMol?
Cheers
Also perhaps useful to consult: 3D functionality in RDkit section https://www.rdkit.org/docs/Cookbook.html
