Beyond Rotatable Bond Counts: Capturing 3D Conformational Flexibility in a Single Descriptor

A new molecular descriptor, nConf20, based on chemical
connectivity, is presented which captures the accessible conformational
space of a molecule. Currently the best available two-dimensional
descriptors for quantifying the flexibility of a particular molecule
are the rotatable bond count (RBC) and the Kier flexibility index.
We present a descriptor which captures this information by sampling
the conformational space of a molecule using the RDKit conformer generator.
Flexibility has previously been identified as a key feature in determining
whether a molecule is likely to crystallize or not. For this application,
nConf20 significantly outperforms previously reported single-variable
classifiers and also assists rule-based analysis of black-box machine
learning classification algorithms.