Beyond Rotatable Bond Counts: Capturing 3D Conformational Flexibility in a Single Descriptor (J.G.P. Wicker and R.I. Cooper)
J. Chem. Inf. Model., 2016, 56 (12), 2347â€“2352 doi: 10.1021/acs.jcim.6b00565
A new molecular descriptor, nConf20, based on chemical connectivity, is presented which captures the accessible conformational space of a molecule. Currently the best available 2-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.