DrugFEATURE: Identifying Druggable Targets by Protein Microenvironments Matching

Druggability of a protein is its potential to be modulated by drug-like molecules. It is important in the target selection phase. We developed DrugFEATURE to quantify druggability by assessing the microenvironments in potential small-molecule binding sites. We benchmarked DrugFEATURE using two data sets. One data set measures druggability using NMR-based screening. DrugFEATURE correlates well with this metric. The second data set is based on historical drug discovery outcomes. Using the DrugFEATURE cutoffs derived from the first, we accurately discriminated druggable and difficult targets in the second. We further identified novel druggable transcription factors with implications for cancer therapy. DrugFEATURE provides useful insight for drug discovery, by evaluating druggability and suggesting specific regions for interacting with drug-like molecules.