Properties and identification of human protein drug targets.
BACKGROUND
We analysed 148 human drug target proteins and 3573 non-drug targets to identify differences in their properties and to predict new potential drug targets.


RESULTS
Drug targets are rare in organelles; they are more likely to be enzymes, particularly oxidoreductases, transferases or lyases and not ligases; they are involved in binding, signalling and communication; they are secreted; and have long lifetimes, shown by lack of PEST signals and the presence of N-glycosylation. This can be summarized into eight key properties that are desirable in a human drug target, namely: high hydrophobicity, high length, SignalP motif present, no PEST motif, more than two N-glycosylated amino acids, not more than one O-glycosylated Ser, low pI and membrane location. The sequence features were used as inputs to a support vector machine (SVM), allowing the assignment of any sequence to the drug target or non-target classes with an accuracy in the training set of 96%. We identified 668 proteins (23%) in the non-target set that have target-like properties. We suggest that drug discovery programmes would be more likely to succeed if new targets are chosen from this set or their homologues.
Bakheet
Tala M
TM
Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Doig
Andrew J
AJ
D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D055808:Drug Discovery; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D020539:Sequence Analysis, Protein
D004364:Pharmaceutical Preparations; D011506:Proteins