title: Beyond Rotatable Bond Counts: Capturing 3D Conformational Flexibility in a Single Descriptor.
abstract: 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, nConf20significantly outperforms previously reported single-variable classifiers and also assists rule-based analysis of black-box machine learning classification algorithms.
authors.affiliation: Chemical Crystallography, University of Oxford , Oxford OX1 3TA, U.K.
authors.forename: Jerome G P
authors.initials: JG
authors.lastname: Wicker
authors.affiliation: Chemical Crystallography, University of Oxford , Oxford OX1 3TA, U.K.
authors.forename: Richard I
authors.identifier: 0000-0001-9651-6308
authors.initials: RI
authors.lastname: Cooper
mesh_terms: D000465:Algorithms; D003460:Crystallization; D015195:Drug Design; D000069550:Machine Learning; D008958:Models, Molecular; D008968:Molecular Conformation