ROCS-derived features for virtual screening

Rapid overlay of chemical structures (ROCS) is a standard tool for the calculation of 3D shape and chemical (“color”) similarity. ROCS uses unweighted sums to combine many aspects of similarity, yielding parameter-free models for virtual screening. In this report, we decompose the ROCS color force field into color components and color atom overlaps , novel color similarity features that can be weighted in a system-specific manner by machine learning algorithms. In cross-validation experiments, these additional features significantly improve virtual screening performance relative to standard ROCS.