ci8b00704_si_001.pdf (2.14 MB)
Conformator: A Novel Method for the Generation of Conformer Ensembles
journal contribution
posted on 2019-02-12, 15:35 authored by Nils-Ole Friedrich, Florian Flachsenberg, Agnes Meyder, Kai Sommer, Johannes Kirchmair, Matthias RareyComputer-aided
drug design methods such as docking, pharmacophore
searching, 3D database searching, and the creation of 3D-QSAR models
need conformational ensembles to handle the flexibility of small molecules.
Here, we present Conformator, an accurate and effective knowledge-based
algorithm for generating conformer ensembles. With 99.9% of all test
molecules processed, Conformator stands out by its robustness with
respect to input formats, molecular geometries, and the handling of
macrocycles. With an extended set of rules for sampling torsion angles,
a novel algorithm for macrocycle conformer generation, and a new clustering
algorithm for the assembly of conformer ensembles, Conformator reaches
a median minimum root-mean-square deviation (measured between protein-bound
ligand conformations and ensembles of a maximum of 250 conformers)
of 0.47 Å with no significant difference to the highest-ranked
commercial algorithm OMEGA and significantly higher accuracy than
seven free algorithms, including the RDKit DG algorithm. Conformator
is freely available for noncommercial use and academic research.