Journal Article

Properties and identification of human protein drug targets

Tala M. Bakheet and Andrew J. Doig

in Bioinformatics

Volume 25, issue 4, pages 451-457
Published in print February 2009 | ISSN: 1367-4803
Published online January 2009 | e-ISSN: 1460-2059 | DOI: https://dx.doi.org/10.1093/bioinformatics/btp002
Properties and identification of human protein drug targets

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Motivation: 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.

Contact: andrew.doig@manchester.ac.uk

Supplementary Information: Supplementary data are available at Bioinformatics online.

Journal Article.  5098 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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