Freely available software for generating 3D coordinates of molecules
Summary: RDKit ETKDG is currently the best open source tool

This is an interesting question, since a reviewer just asked us to do such a benchmark.

The trick is that there's a fine distinction between "generating 3D coordinates" (i.e., one conformation) and "generating 3D coordinates and doing some conformer sampling" presumably with the latter helping to find a low-energy conformer, thermally-accessible ensemble, or a pose that might match an experimental structure or drug docking pose.

I'm not sure there are many papers on the first (i.e., generate one 3D structure - how good is it)? For one, it would depend a lot on your definition of 'good.' I personally prefer 'low energy conformer' because it's easy to define. Most people usually mean 'close to the experimental crystal structure' which is not usually the same as 'lowest energy'.

I digress. There are a few benchmark papers - largely grabbing a few conformers, usually including a mix of free or open source tools and commercial tools.


Ebejer, J.-P.; Morris, G. M.; Deane, C. M. "Freely Available Conformer Generation Methods: How Good Are They?" J Chem Inf Model 2012, 52 (5), 1146–1158.
Friedrich, N.-O.; Meyder, A.; de Bruyn Kops, C.; Sommer, K.; Flachsenberg, F.; Rarey, M.; Kirchmair, J. "High-Quality Dataset of Protein-Bound Ligand Conformations and Its Application to Benchmarking Conformer Ensemble Generators." J Chem Inf Model 2017 57 (3), 529-539.
Nils-Ole Friedrich, Christina de Bruyn Kops, Florian Flachsenberg, Kai Sommer, Matthias Rarey, and Johannes Kirchmair. "Benchmarking Commercial Conformer Ensemble Generators." J Chem Inf Model 2017, 57 (11) , 2719-2728.
Naruki Yoshikawa, Geoffrey R. Hutchison. "Fast, efficient fragment-based coordinate generation for Open Babel" J. Cheminf. 2019 11, art. 49.


While the newest method in Open Babel (development for v3) is faster than RDKit, particularly without using force field minimization, RDKit's ETKDG is very, very good - competitive with most commercial packages.