title: Designing compound subsets: comparison of random and rational approaches using statistical simulation.
abstract: Compound subsets, which may be screened where it is not feasible or desirable to screen all available compounds, may be designed using rational or random selection. Literature on the relative performance of random versus rational selection reports conflicting observations, possibly because some random subsets might be more representative than others and perform better than subsets designed by rational means, or vice versa. In order to address this likelihood, we simulated a large number of rationally designed subsets for evaluation against an equally large number of randomly generated subsets. We found that our rationally designed subsets give higher mean hit rates compared to those of the random ones. We also compared subsets comprising random plates with subsets of random compounds and found that, while the mean hit rate of both is the same, the former demonstrates more variation in the hit rate. The choice of compound file, rational subset method, and ratio of the subset size to the compound file size are key factors in the relative performance of random and rational selection, and statistical simulation is a viable way to identify the selection approach appropriate for a subset.
authors.affiliation: Pfizer Global Research and Development, Sandwich, Kent, UK. kuen.yeap@pfizer.com
authors.forename: Siew Kuen
authors.initials: SK
authors.lastname: Yeap
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Walley
authors.forename: Mike
authors.initials: M
authors.lastname: Snarey
authors.forename: Willem P
authors.initials: WP
authors.lastname: van Hoorn
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Mason
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D015394:Molecular Structure