Protein Engineering, Vol. 14, No. 2, 75-79,
February 2001
© 2001 Oxford University Press
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Using subsite coupling to predict signal peptides
Computer-Aided Drug Discovery, Pharmacia and Upjohn, Kalamazoo, MI 49007-4940, USA. E-mail: kuo-chen.chou{at}am.pnu.com
Given a nascent protein sequence, how can one predict its signal peptide or `Zipcode' sequence? This is a first important problem for scientists to use signal peptides as a vehicle to find new drugs or to reprogram cells for gene therapy. Based on a model that takes into account the coupling effect among some key subsites, the so-called {–3, –1, +1} coupling model, a new prediction algorithm is developed. The overall rate of correct prediction for 1939 secretory proteins and 1440 non-secretary proteins was over 92%. It has not escaped our attention that the new method may also serve as a useful tool for helping investigate further many unclear details regarding the molecular mechanism of the ZIP code protein-sorting system in cells.
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