The statistics of virtual screening and lead optimization

Analytic formulae are used to estimate the error for two virtual screening metrics, enrichment factor and area under the ROC curve. These analytic error estimates are then compared to bootstrapping error estimates, and shown to have excellent agreement with respect to area under the ROC curve and good agreement with respect to enrichment factor. The major advantage of the analytic formulae is that they are trivial to calculate and depend only on the number of actives and inactives and the measured value of the metric, information commonly reported in papers. In contrast to this, the bootstrapping method requires the individual compound scores. Methods for converting the error, which is calculated as a variance, into more familiar error bars are also discussed.