deletions | additions       diff --git a/Discussion.tex b/Discussion.tex  index b98c01d..ecfa7db 100644  --- a/Discussion.tex  +++ b/Discussion.tex 
...
\section*{Discussion}  The MUV dataset, with its focus on eliminating analogue bias, is particularly resistant to single-query shape-based virtual screens \cite{Tiikkainen_2009}. This is reflected in our overall results, shown in Figure~\ref{aucs}, where only two targets (Rho and PKA) achieve AUCs where the 95\% confidence interval does not overlap with 0.5 (random performance). The remaining targets likely lack meaningful whole-molecule shape complementary between the query ligand and the active compounds of the benchmark. One exception may be HIV-rt, where there is clear early enrichment which indicates that a subset of the actives may be compatible with the query molecule.  FOMS dramatically outperformed other methods for the Rho and PKA targets due to correct positioning of a fragment with key, conserved interactions. For reference, comparison,  Figure~\ref{aucs} also shows the performance of a 2D fingerprint, the OpenBabel FP2 \cite{O_Boyle_2011} path-based fingerprint. 2D information is more successful for three targets (ER$\beta$, FXIa, HSP90), and has comparable or worse performance for the remaining targets, illustrating the orthogonality of 2D and 3D approaches. FOMS essentially provides a rapid means of template docking \cite{Ruiz_Carmona_2014,abagyan2015icm,Koes_2012} using shape-based scoring. The disadvantage of fragment-oriented approaches is they are critically dependent on the choice of fragment and its proper positioning in defining the query. Provided these requirements can be met, there are several advantages to shape-based fragment alignment search. By enforcing the fragment alignment, key interaction are guaranteed to be conserved. Previous studies have demonstrated the importance of adding pharmacophoric properties (or `color') to shape similarity \cite{Hawkins_2007}. Fragment alignment introduces a hard bias toward matching a key portion of the query molecule without introducing any additional computation, as required by more general methods. In fact, as we have shown, pre-alignment substantially reduces the computational overhead.