Comparative Performance Assessment of the Conformational Model Generators Omega and Catalyst: A Large-Scale Survey on the Retrieval of Protein-Bound Ligand Conformations

In continuation of our studies to evaluate the ability of various conformer generators to produce bioactive
conformations, we present the extension of our work on the analysis of Catalyst's conformational subsampling
algorithm in a comparative evaluation with OpenEye's currently updated tool Omega 2.0. Our study is
based on an enhanced test set of 778 drug molecules and pharmacologically relevant compounds extracted
from the Protein Data Bank (PDB). We elaborated protocols for two common conformer generation use
cases and applied them to both programs:  (i) high-throughput settings for processing large databases and
(ii) high-quality settings for binding site exploration or lead structure refinement. While Catalyst is faster in
the first case, Omega 2.0 better reproduces the bound ligand conformations from the PDB in less time for
the latter case.