title: Structure-based druggability assessment--identifying suitable targets for small molecule therapeutics.
abstract: A target is druggable if it can be modulated in vivo by a drug-like molecule. The general properties of oral drugs are summarized by the 'rule of 5' which specifies parameters related to size and lipophilicity. Structure-based target druggability assessment consists of predicting ligand-binding sites on the protein that are complementary to these drug-like properties. Automated identification of ligand-binding sites can use geometrical considerations alone or include specific physicochemical properties of the protein surface. Features of a pocket's size and shape, together with measures of its hydrophobicity, are most informative in identifying suitable drug-binding pockets. The recent availability of several validation sets of druggable versus undruggable targets has helped fuel the development of more elaborate methods.
authors.affiliation: Computational Sciences Center of Emphasis, Pfizer Worldwide Research and Development, Cambridge, MA, United States.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Fauman
authors.forename: Brajesh K
authors.initials: BK
authors.lastname: Rai
authors.forename: Enoch S
authors.initials: ES
authors.lastname: Huang
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins; D054852:Small Molecule Libraries