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Liu T, Altman RB. Identifying druggable targets by protein microenvironments matching: application to transcription factors. CPT: Pharmacometrics and Systems Pharmacology. In press. (2014)
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: (1) Known drug-binding sites contain advantageous physicochemical properties for drug binding, or “druggable-microenvironments”; (2) 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 datasets. One dataset measures druggability using NMR-based screening. DrugFEATURE correlates well with this metric. The second dataset 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.


The druggability of a target protein is its potential to be modulated by small, drug-like molecules. Druggability is an important criterion in the target selection phase of drug discovery. However, an effective standard for evaluating target druggability

License: DrugFEATURE

DrugFEATURE is a computational method that evaluates target druggability by assessing the protein microenvironments in potential small molecule binding sites.

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Provides the code for evaluating target druggability

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