Identifying druggable targets by protein microenvironments matching: application to transcription factors.

ABSTRACT: Druggability of a protein is its potential to be modulated by drug-like molecules. It is important in the target selection phase. We hypothesize that: (i) known drug-binding sites contain advantageous physicochemical properties for drug binding, or "druggable microenvironments" and (ii) given a target, the presence of multiple druggable microenvironments similar to those seen previously is associated with a high likelihood of druggability. 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. Usin

SUBMITTER: Liu T 

PROVIDER: S-EPMC3910014 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature