1732 J. Chem. Inf. Model., Vol. 50, No. 9, 2010 CHAN AND LABUTE Figure 9. Flexibly aligning 1TNJ onto 1PPH (carbons in green). Carbons of the correct pose of 1TNJ are in dark blue. Carbons of our solutions (top and bottom: best and second best scoring) are in cyan. According to Proshak et al., when SURFCOMP24 was used with the electrostatic potential, the success rate was 75%. If the lipophilic potential was used, then the success rate was 71%. The method of Cosgrove et al.25 gave a success rate of 50%. The success rate for the authors’ own Shapelets method was 71%. In contrast, our scoring function yielded a success rate of 93%; there were only 2 failed cases out of 28 alignments. One of our failed cases was for aligning 3TMN onto 5TLN. Our result is shown in Figure 3. Our scoring function returned the correct answer as the second best scoring solution (Figure 3, bottom). In any case, our best scoring solution looks highly plausible with heavy overall volumetric overlap as well as the overlap of the aromatic ring and two carbonyl groups (Figure 3, top). Tests were also run on six systems mentioned in Chen et al.,23 where ROCS26 and FLEXS27 were used. An alignment was considered correct if the top scoring solution had a heavy atom rmsd of under 2 Å with the crystallographic overlay. Table 5 gives the overall results for the six systems. Except for the rhinovirus system, which will be examined in more details below, and for the ﬂexible alignment of the CDK2 system, our results are signiﬁcantly better than those obtained by Chen et al. using FLEXS or ROCS. For rigid-body alignments, our fraction of correct results was at least 40% and reached 80% or more in two systems. Naturally, ﬂexible alignment is more difﬁcult than rigid-body alignment, and Figure 10. Flexibly aligning 1TNL onto 1PPH (carbons in green). Carbons of the correct pose of 1TNL are in dark blue. Carbons of our solutions (from top to bottom: ﬁrst, second, and third best scoring) are in cyan. so the percentages of correct results are lower for all systems except rhinovirus (see analysis below). For the CDK2 system, our results for the rigid-body alignments but not for the ﬂexible alignments are signiﬁcantly better than those of Chen et al. using ROCS or FLEXS. CDK2 is a large system (57 ligands) with a complex pharmacophore model.31 If the six ligands 1DI8, 1P5E, 1PKD, 1PXI, 1PXJ, and 1WCC were excluded, then our results would improve from 39.6% to 47.6% correct for the rigid-body alignments and from 22.4% to 26.6% correct for