A. Bonds to monovalent atoms (F, Cl, Br, I, H); B. Bonds to CX3 groups (X=F, Cl, Br, I, H); C. Bonds in small rings and with bond order > 1 The details of the bonds in group C are given in the SI. For these bonds, the dihedral angle (θ) values across all the conformers should have a small standard deviation (σ) and range (η) value. The σ and η parameters were calculated for 9017 sets of dihedrals with a bond order > 1 in the center bond. The 9017 sets of dihedrals were identified using RDKit from 711 molecules in the Hutchison dataset. Box plot analyses were performed on the statistical parameter and the outliers were inspected (Figure and). Certain dihedrals with bonds containing heteroatoms or neighboring to heteroatoms with conjugated characteristics may have abnormally large σ and η. Therefore, these selective bonds are retained during the bond elimination step. The remaining bonds are used to generate a list of dihedral angles, by selecting additional atoms, preferring heteroatoms to carbon and carbons to hydrogen. The elimination criteria do not cover all possible fixed dihedrals. For example, dihedrals within the fused ring and most of dihedrals with conjugated C-X (X = heteroatoms) bonds are fixed. For each dihedral in the list of potentially rotatable dihedrals, dihedral angle values (θ) are calculated for every conformer. The standard deviation and range parameter of these dihedral angle values (σ(θ) and η(θ)) are also computed (Table ). For dihedrals with values of θ close to ±180°, the standard deviation and range are computed from absolute θ (ie σ(|θ|) and η(|θ|)). If these parameters are within the limits given in Table , the dihedral is then labelled as fixed and the associated dihedral angle data is not used as a descriptor.