Descriptor Generation and Selection
The binding affinities of 12 different triptan migraine relief drugs and structurally similar substances to four serotonin receptors, 1B, 1D, h 5-HT1A 1A, and 1F, were identified from published literature (John et al., 1999; Ramadan, Skljarevski, Phebus, & Johnson, 2003). Binding affinities for all four receptors were found for 9 of the compounds. For the other 3 molecules, data were only available for the 1B, 1D, and 1F receptors. Using a variety of programs, specifically, Spartan (Wavefunction Inc., 2020) using parametric method 3 (PM3), PhysChem (ACD/Labs, 2020), EPI Suite (EPA Office of Pollution Prevention Toxics, 2012), and E-Dragon (Tetko et al., 2005; Virtual Computational Chemistry Laboratory, 2005), 1708 descriptors were calculated. All descriptors with less than a 1% standard deviation were eliminated as they were not indicative of the activity differences between the chemicals, leaving 1381 descriptors deemed significant. All molecular descriptors that were calculated can be found in the Supporting Information. These descriptors were entered into SAS JMP 15 (SAS Institute Inc., 2020). Using this program, a stepwise model for each activity was generated. The most significant descriptors by F Ratio before (initial) and after (final) building the model were ranked by highest F Ratio. A selection of this information is presented in Tables 2 and 3.