Interdependence of docking performance and scoring accuracy in virtual screening


Maria Kontoyianni, No affiliation, Plymouth Meeting, PA 19462, Laura McClellan, Pennsylvania State University, University Park, PA 16804, and Glenn Sokol, Drexel University, Philadelphia, PA 19104.
In an effort to uncouple scoring from docking, we first investigated the best known docking programs in their ability to provide solutions similar to the crystallographic modes, by evaluating all of the resultant poses. We then explored whether scoring algorithms can distinguish between accurate and inaccurate poses, provided the accurate poses are available, thus assessing how the docking procedure affects the performance of a virtual screening approach. To evaluate docking, we carried out an extensive computational study in which five docking programs (FlexX, DOCK, GOLD, LigandFit, Glide) were investigated against fourteen protein families (69 targets). Our results indicate that certain algorithms perform consistently better than others, while the active site polarity can be predictive of which program might perform the best. To investigate scoring, we used four docking engines and applied ten scoring functions to the top-ranked docking solutions of seeded databases against six target proteins. The scores of the experimental poses were placed within the total set to assess whether the scoring function required an accurate pose to provide the appropriate rank for the seeded compounds. The LigandFit/Ligscore1 docking/scoring combination provides the most consistent enrichment for all targets studied. We also show that better poses for the docked complexes lead to better scoring function performance, and thus a higher ranking of the active compounds. This means that the enrichment factors would be higher if the experimental poses were available.

Docking and Scoring
9:00 AM-12:20 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- 109B, Oral

Division of Computers in Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004