Baseline performance of the Rosetta energy function prior to recent enhancements.

<p>Each plot compares the performance of two different scoring functions for identifying the active compounds in our virtual screening benchmark. Each of the 18 protein targets corresponds to a single point (<i>green dots</i>); the rank of the active compound (relative to 2500 diverse “decoy” compounds) by each scoring function is indicated. The orange dotted line indicates a ranking of 25, corresponding to the top 1% of the decoy set. <b>(A)</b> FRED’s Chemgauss4 energy function outperforms Rosetta’s original energy function intended for protein-only systems, score12, but not at a statistically significant threshold (p = 0.085). <b>(B)</b> The variant of the score12 energy function that was developed specifically for modeling protein-ligand interactions, score12_ligand, offers improved performance over score12 (p = 0.001). <b>(C)</b> FRED’s Chemgauss4 energy function performs at a similar level as score12_ligand (p = 0.239). All p-values are calculated by applying the Wilcoxon Signed-Rank test to the logs of the ranks (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140359#sec002" target="_blank">Methods</a>).