title: Tautomer enumeration and stability prediction for virtual screening on large chemical databases.
abstract: Tautomeric rearrangements affect the results of cheminformatics applications that depend on the knowledge of the 2D or 3D structure of a compound, such as tools for database searches, fingerprint generation, virtual screening, and physical-chemical properties prediction. In this paper we present TauThor, a tool to enumerate tautomers and predict tautomer stability in the aqueous medium. The enumeration is based on a recursive process that generates tautomers according to the general scheme HX-Y=Z left harpoon over right harpoon X=Y-ZH. The stability of a tautomer is calculated by using a library of 145 fragments associated with experimental tautomeric percentages in water and a pK(a) based-method that utilizes pK(a) values predicted by MoKa. Predicted tautomeric ratios based on pK(a) calculations were benchmarked against literature data for a set of eleven compounds. The FDA approved drugs database, the NCI database and two vendor databases - Specs Screening Library and Asinex Gold Collection - were used to illustrate the impact of tautomerism on chemical libraries and to evaluate the relative occurrences of alternative tautomeric forms.
authors.affiliation: Laboratory for Chemometrics and Cheminformatics, Department of Chemistry, Universita degli Studi di Perugia, via Elce di Sotto 10, 06123 Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Milletti
authors.forename: Loriano
authors.initials: L
authors.lastname: Storchi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sforna
authors.forename: Simon
authors.initials: S
authors.lastname: Cross
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cruciani